Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.14 (
ATP synthase
)
7,042
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
MPV17
is an inner mitochondrial membrane protein whose mutation results in mitochondrial DNA (mtDNA) depletion diseases such as neurohepatopathy.
MPV17
is expressed in several organs including the liver and kidneys. Here, we investigated its role and mechanism of action in cardiac ischemia/reperfusion (I/R) injury. Using isolated hearts from wild type and Mpv17 mutant (Mpv17
mut
) mice, we found that mtDNA levels and normal cardiac function were similar between the groups. Furthermore, reactive oxygen species (ROS) generation, mitochondrial morphology, and calcium levels required to trigger mitochondrial permeability transition pore (mPTP) opening were all similar in normal/non-ischemic animals. However, following I/R, we found that mutant mice had poorer cardiac functional recovery and exhibited more mitochondrial structural damage. We also found that after I/R, Mpv17
mut
heart mitochondria did not produce more ROS than wild type hearts but that calcium retention capacity was gravely compromised. Using immunoprecipitation and mass spectrometry, we identified
ATP synthase
, Cyclophilin D, MIC60 and GRP75 as proteins critical to mitochondrial cristae organization and calcium handling that interact with
MPV17
, and this interaction is reduced by I/R. Together our results suggest that
MPV17
has a protective function in the heart and is necessary for recovery following insults to the heart.
...
PMID:Inner mitochondrial membrane protein MPV17 mutant mice display increased myocardial injury after ischemia/reperfusion. 3277 9
