Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca 2+ Transfer to Mitochondria.

Autor:	Lovy A; Department of Neuroscience, Center for Neuroscience Research, Tufts School of Medicine, Boston, MA, United States.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Ahumada-Castro U; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Bustos G; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Farias P; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Gonzalez-Billault C; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Department of Biology, Faculty of Science, Universidad de Chile, Santiago, Chile., Molgó J; Université Paris-Saclay, CEA, Institut des Sciences du Vivant Frédéric Joliot, ERL CNRS n° 9004, Département Médicaments et Technologies pour la Santé, Service d'Ingénierie Moléculaire pour la Santé (SIMoS), Gif-sur-Yvette, France., Cardenas C; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; The Buck Institute for Research on Aging, Novato, CA, United States.; Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2020 May 25; Vol. 8, pp. 378. Date of Electronic Publication: 2020 May 25 (Print Publication: 2020).
DOI:	10.3389/fcell.2020.00378
Abstrakt:	Mitochondria are highly dynamic organelles constantly undergoing fusion and fission. Ca 2+ regulates many aspects of mitochondrial physiology by modulating the activity of several mitochondrial proteins. We previously showed that inhibition of constitutive IP3R-mediated Ca 2+ transfer to the mitochondria leads to a metabolic cellular stress and eventually cell death. Here, we show that the decline of mitochondrial function generated by a lack of Ca 2+ transfer induces a DRP-1 independent mitochondrial fragmentation that at an early time is mediated by an increase in the NAD+/NADH ratio and activation of SIRT1. Subsequently, AMPK predominates and drives the fragmentation. SIRT1 activation leads to the deacetylation of cortactin, favoring actin polymerization, and mitochondrial fragmentation. Knockdown of cortactin or inhibition of actin polymerization prevents fragmentation. These data reveal SIRT1 as a new player in the regulation of mitochondrial fragmentation induced by metabolic/bioenergetic stress through regulating the actin cytoskeleton. (Copyright © 2020 Lovy, Ahumada-Castro, Bustos, Farias, Gonzalez-Billault, Molgó and Cardenas.)
Databáze:	MEDLINE
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