Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca²⁺ Transfer to Mitochondria.

ABSTRACT: Mitochondria are highly dynamic organelles constantly undergoing fusion and fission. Ca²⁺ regulates many aspects of mitochondrial physiology by modulating the activity of several mitochondrial proteins. We previously showed that inhibition of constitutive IP3R-mediated Ca²⁺ 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 Ca²⁺ 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, a

SUBMITTER: Lovy A 

PROVIDER: S-EPMC7261923 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature