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The Requirement of Cytochrome c Oxidase for Mitochondrial Fusion in Copper‐induced Regression of Cardiomyocyte Hypertrophy
Author(s) -
Yin Wen,
Li Rui,
Feng Xiaorong,
Kang Y. James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1015.5
Subject(s) - cytochrome c oxidase , muscle hypertrophy , mitochondrion , medicine , microbiology and biotechnology , fragmentation (computing) , cytochrome c , biology , endocrinology , chemistry , ecology
Copper (Cu) supplementation reverses cardiomyocyte hypertrophy along with recovery of cytochrome c oxidase (CCO) activity and morphology of mitochondria. The present study was undertaken to test the hypothesis that Cu induces recovery of mitochondrial morphology by regulating CCO activity in hypertrophic cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 mM in cultures for 48 hrs to induce cell hypertrophy. Depressed CCO activity and fragmentation of mitochondria were observed in the hypertrophic cardiomyocytes. Cu addition to the cultures of hypertrophic cardiomyocytes at a final concentration of 5 mM for 24 hrs recovered CCO activity and led to mitochondrial fusion, along with regression of cell hypertrophy. Depression of CCO activity by siRNA targeting CCO assembly homolog 17 (COX17), a Cu chaperone for CCO, led to fragmentation of mitochondria. The COX17 deficiency‐mediated CCO depression suppressed Cu‐induced mitochondrial fusion, along with an irreversibility of cell hypertrophy. This study thus demonstrates that CCO is required for mitochondrial fusion, which is critically involved in the Cu‐induced regression of cardiomyocyte hypertrophy. Support or Funding Information Supported by National Science Foundation of China (NSFC grant 81230004).