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SIRT3 Deacetylatesand Activates OPA1 ToRegulateMitochondrialDynamics duringStress Sadhana SamantHannah J. ZhangZhigang Hong2013 год

SIRT3 Deacetylates and Activates OPA1 To Regulate Mitochondrial Dynamics during Stress
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Аннотация: Mitochondrial morphology is regulated by the balance between two counteracting mitochondrial processes of fusion and fission. There is significant evidence suggesting a stringent association between morphology and bioenergetics of mitochondria. Morphological alterations in mitochondria are linked to several pathological disorders, including cardiovascular diseases. The consequences of stress-induced acetylation of mitochondrial proteins on the organelle morphology remain largely unexplored. Here we report that OPA1, a mitochondrial fusion protein, was hyperacetylated in hearts under pathological stress and this posttranslational modification reduced the GTPase activity of the protein. The mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating its GTPase activity. Mass spectrometry and mutagenesis analyses indicated that in SIRT3-deficient cells OPA1 was acetylated at lysine 926 and 931 residues. Overexpression of a deacetylation-mimetic version of OPA1 recovered the mitochondrial functions of OPA1-null cells, thus demonstrating the functional significance of K926/931 acetylation in regulating OPA1 activity. Moreover, SIRT3-dependent activation of OPA1 contributed to the preservation of mitochondrial networking and protection of cardiomyocytes from doxorubicin-mediated cell death. In summary, these data indicated that SIRT3 promotes mitochondrial function not only by regulating activity of metabolic enzymes, as previously reported, but also by regulating mitochondrial dynamics by targeting OPA1.
Год издания: 2013
Авторы: Sadhana Samant, Hannah J. Zhang, Zhigang Hong, Vinodkumar B. Pillai, Nagalingam R. Sundaresan, Donald J. Wolfgeher, Stephen L. Archer, David C. Chan, Mahesh P. Gupta
Издательство: Taylor & Francis
Источник: Molecular and Cellular Biology
Ключевые слова: Mitochondrial Function and Pathology, ATP Synthase and ATPases Research, Sirtuins and Resveratrol in Medicine
Другие ссылки: Molecular and Cellular Biology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
CaltechAUTHORS (California Institute of Technology) (PDF)
CaltechAUTHORS (California Institute of Technology) (HTML)
PubMed Central (HTML)
PubMed (HTML)