RGD Reference Report - Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury. - Rat Genome Database

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Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury.

Authors: Zhang, Weilin  Ren, He  Xu, Chunling  Zhu, Chongzhuo  Wu, Hao  Liu, Dong  Wang, Jun  Liu, Lei  Li, Wei  Ma, Qi  Du, Lei  Zheng, Ming  Zhang, Chuanmao  Liu, Junling  Chen, Quan 
Citation: Zhang W, etal., Elife. 2016 Dec 20;5. pii: e21407. doi: 10.7554/eLife.21407.
RGD ID: 12738374
Pubmed: PMID:27995894   (View Abstract at PubMed)
PMCID: PMC5214169   (View Article at PubMed Central)
DOI: DOI:10.7554/eLife.21407   (Journal Full-text)

Mitochondrial dysfunction underlies many prevalent diseases including heart disease arising from acute ischemia/reperfusion (I/R) injury. Here, we demonstrate that mitophagy, which selectively removes damaged or unwanted mitochondria, regulated mitochondrial quality and quantity in vivo. Hypoxia induced extensive mitochondrial degradation in a FUNDC1-dependent manner in platelets, and this was blocked by in vivo administration of a cell-penetrating peptide encompassing the LIR motif of FUNDC1 only in wild-type mice. Genetic ablation of Fundc1 impaired mitochondrial quality and increased mitochondrial mass in platelets and rendered the platelets insensitive to hypoxia and the peptide. Moreover, hypoxic mitophagy in platelets protected the heart from worsening of I/R injury. This represents a new mechanism of the hypoxic preconditioning effect which reduces I/R injury. Our results demonstrate a critical role of mitophagy in mitochondrial quality control and platelet activation, and suggest that manipulation of mitophagy by hypoxia or pharmacological approaches may be a novel strategy for cardioprotection.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypoxia severityISOFundc1 (Mus musculus)12738374; 12738374 RGD 
Hypoxia severityIMP 12738374 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fundc1  (FUN14 domain containing 1)

Genes (Mus musculus)
Fundc1  (FUN14 domain containing 1)

Genes (Homo sapiens)
FUNDC1  (FUN14 domain containing 1)


Additional Information