RGD Reference Report - MAP4 mechanism that stabilizes mitochondrial permeability transition in hypoxia: microtubule enhancement and DYNLT1 interaction with VDAC1. - Rat Genome Database

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MAP4 mechanism that stabilizes mitochondrial permeability transition in hypoxia: microtubule enhancement and DYNLT1 interaction with VDAC1.

Authors: Fang, Ya-dong  Xu, Xue  Dang, Yong-ming  Zhang, Yi-ming  Zhang, Jia-ping  Hu, Jiong-yu  Zhang, Qiong  Dai, Xia  Teng, Miao  Zhang, Dong-xia  Huang, Yue-sheng 
Citation: Fang YD, etal., PLoS One. 2011;6(12):e28052. doi: 10.1371/journal.pone.0028052. Epub 2011 Dec 2.
RGD ID: 13208528
Pubmed: PMID:22164227   (View Abstract at PubMed)
PMCID: PMC3229508   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0028052   (Journal Full-text)

Mitochondrial membrane permeability has received considerable attention recently because of its key role in apoptosis and necrosis induced by physiological events such as hypoxia. The manner in which mitochondria interact with other molecules to regulate mitochondrial permeability and cell destiny remains elusive. Previously we verified that hypoxia-induced phosphorylation of microtubule-associated protein 4 (MAP4) could lead to microtubules (MTs) disruption. In this study, we established the hypoxic (1% O(2)) cell models of rat cardiomyocytes, H9c2 and HeLa cells to further test MAP4 function. We demonstrated that increase in the pool of MAP4 could promote the stabilization of MT networks by increasing the synthesis and polymerization of tubulin in hypoxia. Results showed MAP4 overexpression could enhance cell viability and ATP content under hypoxic conditions. Subsequently we employed a yeast two-hybrid system to tag a protein interacting with mitochondria, dynein light chain Tctex-type 1 (DYNLT1), by hVDAC1 bait. We confirmed that DYNLT1 had protein-protein interactions with voltage-dependent anion channel 1 (VDAC1) using co-immunoprecipitation; and immunofluorescence technique showed that DYNLT1 was closely associated with MTs and VDAC1. Furthermore, DYNLT1 interactions with MAP4 were explored using a knockdown technique. We thus propose two possible mechanisms triggered by MAP4: (1) stabilization of MT networks, (2) DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiac muscle cell apoptotic process  IMP 13208528 RGD 
negative regulation of mitochondrial membrane permeability  IMP 13208528 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dynlt1  (dynein light chain Tctex-type 1)


Additional Information