Acute and chronic mitochondrial respiratory chain deficiency differentially regulate lysosomal biogenesis.

ABSTRACT: Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial signaling affects other organelles, particularly lysosomes. Here, we demonstrate that mitochondrial respiratory chain (RC) impairments elicit a stress signaling pathway that regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, the effect of mitochondrial stress over lysosomal biogenesis depends on the timeframe of the stress elicited: while RC inhibition with rotenone or uncoupling with CCCP initially triggers lysosomal biogenesis, the effect peaks after few hours and returns to baseline. Long-term RC inhibition by long-term treatment with rotenone, or patient mutat

SUBMITTER: Fernandez-Mosquera L 

PROVIDER: S-EPMC5366864 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature