Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.

ABSTRACT: Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity of the lysosomal Ca²⁺ channel MCOLN1 (mucolipin 1). MCOLN1 is regulated by phosphoinositide kinase PIKFYVE and its product PtdIns(3,5)P₂, which is also decreased in

SUBMITTER: Fernandez-Mosquera L 

PROVIDER: S-EPMC6693470 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature