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lördag 25 januari 2020

PI4L IIIbeta

2012 Mar 9;287(11):8457-67. doi: 10.1074/jbc.M111.312561. Epub 2012 Jan 17.

Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.


Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.

Joitain PI4KIIIbeta inhibittoreita on olemassa.

måndag 23 december 2019

ZFYFE- mappi sisältää 31 ZFYVE proteiinista tietoa

Muistiin  omalle tietokoneelle 23.12.2019
Nämä proteiinit pitää käydä yksityiskohtaisesti läpi, koska ne tekevät interaktiota  fosfoinositidilipidien (PI)  kanssa.

En voi kopioida niitä suoraan tähän.

FYVE domeenin merkityksestä (2015) : FYVE DOMEENIN MERKITYKSESTÄ: Elife. 2015 May 18;4.
 doi: 10.7554/eLife.06041
linkkii spesifisesti  mRNA-kuljetuksen endosomaaliseen liikenteeseen
 A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking. Pohlmann T1, Baumann S1, Haag C1, Albrecht M2, Feldbrügge M1.

 Solussa tapahtuvasta kuljetustoiminnasta  on kertyvää aihepiiriä mRNA:n ja kalvokuljetuksen välisestä läheisestä yhteydestä.  Näkyvä esimerkki on  mikrotubuluksista riippuvan lähettiRNA:n  ja siihen assosioituvien ribosomien kuljetus endosomeissa. Tämä koordinoitu prosessi on ratkaiseva  septiinifilamentoitumisen  asianmukaisuudelle ja polarisoituneiden solujen tehokkaalle kasvulle.  kuten esim  sienirihmoissa ( fungal hyphae).

  •  An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae.
Vaikka on olemassa yksityiskohtaista tietoa  avainasemassa olevista RNA:ta sitovista proteiineista ja  prosessiin osallistuvista molekulaarisista moottoreista, on ollut kuitenkin epäselvää, millä tavalla mRNA- proteiinit ovat kalvoihin liittyneinä kuljetuksen aikana.  Tässä työssään tutkijat identifioivat erään uuden FYVE-sinkkisormidomeenin  sisältävän tekijän, joka  tekee interaktiota endosomaalisiin lipideihin  ja erään uuden  PAM2-kaltaisen domeenin, jota vaatii interaktio  RNA:ta sitovan avainproteiinin MLLE-domeenin kanssa.
  •  Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein.
 Johdonmukaisesti tämän  FYVE-domeeninomaavan proteiinin puuttuminen johtaa  sepsifisiin puutoksiin mRNA-. ribosomi- ja septiinikuljetuksissa, muta  ei vaikuta  endosomien  yleisfunktioihin eikä niiden liikkumisiin.

  •  Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement.
 Täten  tämä on ensimmäinen endosomaalinen komponentti, joka on spesifinen mRNP:n kuljetukselle
mikä   tuo valoon erään uuden mekanimsin, joka kytkee  mRNP:n endosomeihin.

Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.
 Ustilago maydis;
 cell biology;
 infectious disease;
 mRNA transport;
 Trafficking of membranes is essential for intracellular logistics. Important membranous carriers are endosomes that transport lipids, proteins, and mRNAs. These large vesicular structures are well-known for their function in endocytosis, transporting plasma membrane proteins to their site of degradation in the lysosome/vacuole system (Huotari and Helenius, 2011; Rusten et al., 2012). However, they also carry out other functions, such as receptor recycling or cytoplasmic signalling, and are therefore considered to be multipurpose platforms (Gould and Lippincott-Schwartz, 2009). Early endosomes (EE) are characterised by the presence of Rab5-like small G proteins and their special lipid composition consisting of PI3P lipids (phosphatidylinositol 3-phosphate; Stenmark et al., 2002; Kutateladze, 2006). These lipids are recognised by distinct protein domains, such as the FYVE zinc finger (Stenmark et al., 1996).

 Endosomes are actively transported along the microtubule cytoskeleton, which is particularly critical in highly polarised cells, such as neurons and fungal hyphae. In the latter, microtubule-dependent transport supports apical tip growth and secretion of hydrolytic enzymes. This process is streamlined for efficiency and defects in transport result in impaired polar growth and reduced fitness (Peñalva et al., 2012; Riquelme and Sánchez-León, 2014).
Key factors are RNA-binding proteins that recognise specific localisation sequences within target mRNAs. Together with accessory factors, such as the poly(A)-binding protein, they form large macromolecular complexes called mRNPs (messenger ribonucleoprotein particles, Bullock, 2011; Eliscovich et al., 2013;
 The best fungal model system to study co-trafficking of endosomes and mRNAs is the corn pathogen Ustilago maydis (Jansen et al., 2014). Here, the switch from yeast-like to hyphal growth is essential for the infection of its host, and defects in this polar growth correlate with reduced fungal virulence (Brefort et al., 2009; Vollmeister et al., 2012a). In hyphae, endosomes shuttle extensively along the microtubule cytoskeleton throughout the entire length of the hyphae (Steinberg, 2014). Transport is mediated by a cytoplasmic dynein complex (Straube et al., 2001) transporting Rab5a-positive endosomes towards the microtubule minus-ends and the kinesin-3 type motor Kin3 transports in the opposite direction (plus-ends)  (Schuster et al., 2011). Since endosomes carry the SNARE Yup1 (soluble N-ethylmaleimide-sensitive-factor attachment receptor; Wedlich-Söldner et al., 2000) and are positive for Rab5a, they were classified as early endosomes, which have initially been proposed to mainly function in endocytosis and signalling (Steinberg, 2012; Bielska et al., 2014).
 Recently, we discovered a novel function for these endosomes, namely mRNA transport throughout the hyphae (Baumann et al., 2012), a process that is critical for polar growth and unconventional secretion of the endochitinase Cts1 (Becht et al., 2006; Koepke et al., 2011). The key factor is the RNA-binding protein Rrm4 containing three N-terminal RRMs (RNA recognition motifs) for RNA-binding and two C-terminal PABC/MLLE domains (Figure 1A; Becht et al., 2005; Zarnack and Feldbrügge, 2010; Baumann et al., 2012; Vollmeister et al., 2012b). The latter is known from the cytoplasmic poly(A)-binding protein and functions as a binding pocket for peptides containing a PAM2 motif (PABP-interacting motif 2; Albrecht and Lengauer, 2004; Kozlov et al., 2004; Jinek et al., 2010; Xie et al., 2014).

Rrm4 specifically associates with shuttling Rab5a-positive endosomes (Baumann et al., 2012) and binds a specific set of mRNAs encoding, for example, the small G protein Rho3 or the septin Cdc3 (König et al., 2009). Studying Cdc3 in more detail revealed that not only its mRNA but also the protein is transported on endosomes in an Rrm4-dependent manner suggesting that endosome-coupled translation is crucial for septin localisation on these membranous carriers and needed for septin filamentation (Baumann et al., 2014). This was verified by demonstrating that translationally active ribosomes are transported on endosomes (Higuchi et al., 2014).
 In addition to the PAM2 motif (Figure 1B) and the FYVE domain, it contained five ankyrin repeats known to be protein–protein interaction interfaces (Al-Khodor et al., 2010), and a RING domain involved in ubiquitination (Figure 1A). The protein was designated Upa1 for the U. maydis PAM2 protein.

A novel FYVE domain protein containing PAM2 and PAM2L motifs for interaction with different MLLE proteins
Aiming at the identification of endosomal components involved in mRNP transport, the PAM2 protein Upa1 caught our attention because of its FYVE and RING domains. This domain organisation is similar to Pib1p in S. cerevisiae and mammalian Rififylin, two proteins which appear to function in endosomal protein sorting. Although their precise roles are still unclear (Shin et al., 2001; Coumailleau et al., 2004), they might function in ubiquitination during protein sorting due to the presence of the RING domain found in RNF-type E3 ubiquitin ligases (Nikko and Pelham, 2009).

Official Symbol
RFFLprovided by HGNC
Official Full Name
ring finger and FYVE like domain containing E3 ubiquitin protein ligase
Also known as
Ubiquitous expression in thyroid (RPKM 18.0), esophagus (RPKM 12.3) and 25 other tissues See more
 Huomaan aiemmasta  RNF- luettelosta  jostain syystä samaan funktionaaliseen  ryhmään merkattujani:

(a) RNF34,( kr.12q24.31) ,  CARP-1. RIF, RIFF ,  "MOMO" Preferred Names
E3 ubiquitin-protein ligase RNF34
FYVE-RING finger protein MOMO  ( Expr. Brain Grey matter)
RING finger protein RIFF
RING-type E3 ubiquitin transferase RNF34
caspase regulator CARP1
caspases-8 and -10-associated RING finger protein 1
human RING finger homologous to inhibitor of apoptosis protein
ring finger protein 34, E3 ubiquitin protein ligase
Esim: Termogeneesin säätely: RNF34  säätää negatiivisesti  kylmän aktivoimaa  ruskean rasvan  uncoupling factor proteiinia.

(b) RNF45, AMFR, (16q13) Autocrine motility factor receptor  gp78. Tumour motility stimulating protein.
Conserved Domains (3) summary
CUE_AMFR; CUE domain found in autocrine motility factor receptor (AMFR) and similar proteins
RING-H2_AMFR; RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins
zf-rbx1; RING-H2 zinc finger domain

(c) RNF145,( 5q33.3). Hajoittaa  HMGCR yhdessä ubikitiinilig. gp78 kanssa)
Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase. Jiang LY, et al. J Biol Chem, 2018 Mar 16. PMID 29374057, Free PMC Article

  NP_001186309.1  RING finger protein 145 isoform 1
Conserved Domains (3) summary

zf-rbx1; RING-H2 zinc finger
zf-RING_2; Ring finger domain
TRC8_N; TRC8 N-terminal domain
TRC8 N-terminal domain
This region is found at the N-terminus of the TRC8 protein. TRC8 is an E3 ubiquitin-protein ligase also known as RNF139. This region contains 12 transmembrane domains. This region has been suggested to contain a sterol sensing domain. It has been found that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG.

(d) RNF189, RFFL, Rififylin, CARP-2, FRING, 17q12.  "SAKURA"
Sydämen repolarisaatiossa merkitsevä.  (QT)  
Preferred Names
E3 ubiquitin-protein ligase rififylin
FYVE-RING finger protein SAKURA ( Expr. Brain White matter and  periph. organs)
RING finger and FYVE-like domain-containing protein 1
RING finger protein 189
RING-type E3 ubiquitin transferase rififylin
caspase 8 and 10 associated RING protein-2
caspase regulator CARP2
caspases-8 and -10-associated RING finger protein 2
ring finger and FYVE-like domain containing 1
NP_001017368.1  E3 ubiquitin-protein ligase rififylin
Conserved Domains (3) summary
FYVE_CARP2; FYVE-like domain found in caspase regulator CARP2 and similar proteins
zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NYAP_N; Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter
Katson FYVE - Znf finger proteiinista SAKURA nimeltään tietoa:

2003 Aug;86(3):749-62.
A palmitoylated RING finger ubiquitin ligase and its homologue in the brain membranes.
Ubiquitin (Ub) ligation is implicated in active protein metabolism and subcellular trafficking and its impairment is involved in various neurologic diseases. In rat brain, we identified two novel Ub ligases, Momo and Sakura, carrying double zinc finger motif and RING finger domain. Momo expression is enriched in the brain gray matter and testis, and Sakura expression is more widely detected in the brain white matter as well as in many peripheral organs. Both proteins associate with the cell membranes of neuronal and/or glial cells. We examined their Ub ligase activity in vivo and in vitro using viral expression vectors carrying myc-tagged Momo and Sakura. Overexpression of either Momo or Sakura in mixed cortical cultures increased total polyubiquitination levels. In vitro ubiquitination assay revealed that the combination of Momo and UbcH4 and H5c, or of Sakura and UbcH4, H5c and H6 is required for the reaction. Deletion mutagenesis suggested that the E3 Ub ligase activity of Momo and Sakura depended on their C-terminal domains containing RING finger structure, while their N-terminal domains influenced their membrane association. In agreement, Sakura associating with the membrane was specifically palmitoylated. Although the molecular targets of their Ub ligation remain to be identified, these findings imply a novel function of the palmitoylated E3 Ub ligase(s).

Siirsin Veri ja hyytyminen blogiin viitteen 27.12. 2019.

onsdag 18 december 2019

ZFYVE29 on PIP5K! Myös nimi PIKFYVE

ZFYVE29, PIKFYVE (2q34).Yllättävää! Tämä on fosfatiyyli-inositidi-kinaasi PIP5K, PIP5K3.  Asetan  Phytin- blogiini. geni ekspressoituu luuytimessä ja imusolmukkeessa.

Also known as
Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]
Ubiquitous expression in bone marrow (RPKM 9.7), lymph node (RPKM 8.9) and 25 other tissues See more

 Onko APP:llä fysiologinen funktio? On. Se kontrolloi PIFYVE. 

2015 Jun 30;10(6):e0130485. doi: 10.1371/journal.pone.0130485. eCollection 2015.

The Amyloid Precursor Protein Controls PIKfyve Function.

Aston University, School of Life and Health Sciences, Aston Triangle, Birmingham, B4 7ET, United Kingdom.
Biotechnologisches Zentrum, TU-Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom.Abstract
While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease.

måndag 28 oktober 2019

Fosfolipidit autofagosomin muodostuksessa ja fuusiossa

Journal of Molecular Biology
Volume 428, Issue 24, Part A, 4 December 2016, Pages 4819-4827
Phospholipids in Autophagosome Formation and Fusion
Under a Creative Commons license


Phosphoinositides (PI)  regulate the initiation and elongation of isolation membranes.
Lipids with small headgroups and, in particular, phosphatidylethanolamine (PE)  are likely to play important roles during autophagosome formation.
The generation and specific turnover of phosphoinositides (PI) on autophagosomal and lysosomal membranes regulate fusion.
The lipid composition of isolation membranes and autophagosomes is currently unknown.


Autophagosomes are double-membrane organelles that are formed during a process referred to as macroautophagy. They serve to deliver cytoplasmic material into the lysosome for degradation. Autophagosomes are formed in a de novo manner and are the result of substantial membrane remodeling processes involving numerous protein–lipid interactions. While most studies focus on the proteins involved in autophagosome formation, it is obvious that lipids including phospholipids, sphingolipids, and sterols play an equally important role. Here, we summarize the current knowledge about the role of lipids, especially focusing on phospholipids and their interplay with the autophagic protein machinery during autophagosome formation and fusion.

lördag 26 oktober 2019

PI3K säätelyllinen alayksikkö silppuroituu BTB- Kelch perheen proteiinista KBTBD2

Also known as
Ubiquitous expression in gall bladder (RPKM 16.7), bone marrow (RPKM 14.7) and 25 other tissues See more
2016 Oct 18;113(42):E6418-E6426. Epub 2016 Oct 5.
Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice.
We describe a metabolic disorder characterized by lipodystrophy, hepatic steatosis, insulin resistance, severe diabetes, and growth retardation observed in mice carrying N-ethyl-N-nitrosourea (ENU)-induced mutations. The disorder was ascribed to a mutation of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) and was mimicked by a CRISPR/Cas9-targeted null allele of the same gene. Kbtbd2 encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase. KBTBD2 targeted p85α, the regulatory subunit of the phosphoinositol-3-kinase (PI3K) heterodimer, causing p85α ubiquitination and proteasome-mediated degradation. In the absence of KBTBD2, p85α accumulated to 30-fold greater levels than in wild-type adipocytes, and excessive p110-free p85α blocked the binding of p85α-p110 heterodimers to IRS1, interrupting the insulin signal. Both transplantation of wild-type adipose tissue and homozygous germ line inactivation of the p85α-encoding gene Pik3r1 rescued diabetes and hepatic steatosis phenotypes of Kbtbd2-/- mice. Kbtbd2 was down-regulated in diet-induced obese insulin-resistant mice in a leptin-dependent manner. KBTBD2 is an essential regulator of the insulin-signaling pathway, modulating insulin sensitivity by limiting p85α abundance.


Kbtbd2; diabetes; insulin resistance; p85α; ubiquitination

torsdag 3 oktober 2019

Aivojen alueen lipidistruktuurissa on havaittu AD taudissa varhain kardiolipiinin muutoksia synaptisissa mitokondrioissa.

Kardiolipiini eroaa  muista fosfolipidirakenteista olennaisesti ja sen toimintapaikka on tosiaankin  vain mitokodnria, jolla on erikoinen kalvorakenne, ulko kalvo ja sisäkalvo ja niitten välille jäänyt  enregiatarkoituksiin tärkeä  tila. Ulkokalvolla ja sisäkalvolla on  erilaiset fosfolipidikoostumat.
KARDIOLIPIINI  on tosi moduli joka on kondensoitu kolmesta  glyserolirungosta. R tarkoittaa rasvahappoa.
Kuva  Bildresultat för Cardiolipin

  • Metabolisia mitokondrioita on tutkittu 2014, kardiolipiini, joka on mitokondrain sisäkalvossa.  Kardiolipiinirakenteeseen vaikuttaa ihmisen elintapa ja dieetti ainakin osaltaan,  herediteetti on tietysti  vahvin vaikuttaja. muta ihminen voi  elintavoillaan haitata kardiolipiinirakenteen  pätevyyttä. Ala on yksi linkki, josas on kuvattu mitokondrian ulompaa kaksoislipidikerrosta joka suojaa  sisäossaa, jonka ympärillä on poimuinen lipidikerros, ja siinä sisäkerroksessa on kardiolipiinin sijaintipaikka.  Siihen sisäkerrokseen asettu kellumaan  tämän "energialaitoksen" proteiiniketju, "hengitysketju" , joka  kuljttaa elektroneja ja ottaa vastaan happea, tekee   radikaalimuotoista  happea  ja muodostaa  vesimolekyyliä, metabolista  vettä H2O.  ATP-pakkauksia tekevä järjestelmä sijaitsee myös  siinä.  Tuottuvia protoneja  syötetään kalvovälitilaan ja sieltä ne virtaavat  alas ja  nergia otetaan fosfaattisidoksiin  proiteiinissa : ATP-pakkauksiin.  
  •  Alustana  tälle järjestelmälle täytyy olla  normaalia kardiolipiiniä.

2014 Oct;46(5):447-57. doi: 10.1007/s10863-014-9555-y. Epub 2014 Jun 21.
Impact of high dietary lipid intake and related metabolic disorders on the abundance and acyl composition of the unique mitochondrial phospholipid, cardiolipin.
UMR 866, Dynamique Musculaire et Métabolisme, Centre INRA de Montpellier, 34060, Montpellier,Abstract
Excessive dietary lipid intake, coupled with lack of exercise, are the major causes of the development and progression of metabolic syndrome features e. g. obesity, hepatic steatosis, insulin resistance, type 2 diabetes and cardiovascular diseases. These metabolic diseases are associated with both structural and functional alterations of mitochondria.  
Cardiolipin (CL) is a unique phospholipid that is almost exclusively localized in the mitochondrial inner membrane.

 Cardiolipin is at the heart of mitochondrial metabolism playing a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics, and in many of the mitochondrial-dependent steps of apoptosis. Indeed, alterations to CL content and acyl chain profile have been associated with mitochondrial dysfunction in multiple tissues in Barth syndrome and in many other physio-pathological conditions. After a brief overview of the biological roles of CL, we highlight the consequences of lipid overload-related nutritional manipulations as well as related metabolic disorders on both CL content and its fatty acid composition in the major metabolic tissues, the heart, muscle and liver. The goal of this review is to fill a void in the CL literature concerning the effects of CL abundance and form that arise following high lipid supplementation and the related metabolic disorders.
[Indexed for MEDLINE] 

  •  Viime vuodelta löytyy selvitystä kardiolipidin molekulaarisesta  koostumuskesta.
2018 Apr 17;115(16):4158-4163. doi: 10.1073/pnas.1719407115. Epub 2018 Apr 4.

Molecular structural diversity of mitochondrial cardiolipins.Oemer G1, Lackner K1, Muigg K1, Krumschnabel G2, Watschinger K3, Sailer S3, Lindner H4, Gnaiger E2, Wortmann SB5,6, Werner ER3, Zschocke J1, Keller MA7.Abstract

cardiolipin; lipids; mass spectrometry; mathematical modeling; mitochondria
[Indexed for MEDLINE]
Free PMC Article
  • ENTÄ SITtEN AIVOJEN mitokondrioitten kardiolipiinin piirteet?

    2015;43(4):1375-92. doi: 10.3233/JAD-141002.

    Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer's disease.

    l. Abstract
    Brain mitochondria are fundamental to maintaining healthy functional brains, and their dysfunction is involved in age-related neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we conducted a research on how both non-synaptic and synaptic mitochondrial functions are compromised at an early stage of AD-like pathologies and their correlation with putative changes on membranes lipid profile, using 3 month-old nontransgenic and 3xTg-AD mice, a murine model of experimental AD. Bioenergetic dysfunction in 3xTg-AD brains is evidenced by a decrease of brain ATP levels resulting, essentially, from synaptic mitochondria functionality disruption as indicated by declined respiratory control ratio associated with a 50% decreased complex I activity. Lipidomics studies revealed that synaptic bioenergetic deficit of 3xTg-AD brains is accompanied by alterations in the phospholipid composition of synaptic mitochondrial membranes, detected either in phospholipid class distribution or in the phospholipids molecular profile. Globally, diacyl- and lyso-phosphatidylcholine lipids increase while ethanolamine plasmalogens and cardiolipins content drops in relation to nontransgenic background
     However, the main lipidomic mark of 3xTg-AD brains is that cardiolipin cluster-organized profile is lost in synaptic mitochondria due to a decline of the most representative molecular species.
    In contrast to synaptic mitochondria, results support the idea that non-synaptic mitochondria function is preserved at the age of 3 months. Although the genetically construed 3xTg-AD mouse model does not represent the most prevalent form of AD in humans, the present study provides insights into the earliest biochemical events in AD brain, connecting specific lipidomic changes with synaptic bioenergetic deficit that may contribute to the progressive synapses loss and the neurodegenerative process that characterizes AD. KEYWORDS:
    Alzheimer's disease; brain bioenergetics; cardiolipin; mitochondrial lipidomics.