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Mitophagy and Cardioprotection
Author(s) -
Gottlieb Roberta A.
Publication year - 2013
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.27.1_supplement.449.3
Subject(s) - mitophagy , cardioprotection , autophagy , parkin , coenzyme q10 , pharmacology , sirtuin , resveratrol , pravastatin , pi3k/akt/mtor pathway , chemistry , microbiology and biotechnology , medicine , biology , ischemia , biochemistry , signal transduction , cholesterol , apoptosis , nad+ kinase , disease , parkinson's disease , enzyme
Cardiomyocytes rely on autophagy for cellular homeostasis and as a response to nutritional, oxidative, or ischemic stress. Mitophagy, an organelle‐selective form of autophagy, is invoked in the heart in response to cardioprotective interventions such as ischemic preconditioning. An essential regulator of mitophagy is Parkin. Recent work has demonstrated a requirement for Parkin‐dependent mitophagy in the cardioprotection mediated by ischemic preconditioning. Given that autophagy is suppressed in the setting of metabolic syndrome, and given that statins are widely administered to patients with metabolic syndrome, we investigated the effects of statins on autophagy, mitophagy, and cardioprotection. We found that statins induced autophagy through inhibition of mTOR signaling, and induced mitophagy through a Parkin‐dependent pathway. Statin‐mediated cardioprotection was abolished in Parkin‐null mice. Like cholesterol, coenzyme Q10 is a downstream product of HMG‐CoA reductase. Cell‐based studies showed that statin‐dependent mitophagy was abolished by supplementation with coenzyme Q10. Acute supplementation of coenzyme Q10 in mice abolished the cardioprotective effects of statins, raising concern that this widely‐used nutritional supplement could interfere with the cardioprotective benefits of statin therapy.