Damage-Sensing in Mitochondrial Disorders: From Mitophagy to the Integrated Stress Response

We are pleased to announce that Professor Derek Narendra from National Institutes of Health, USA will join Targeting Mitochondria 2026 as a speaker.

Summury:

The presentation will focus on how mitochondria-damage sensing pathways are coordinated in degenerative neurological disorders. Mitochondria have internal sensors of mitochondrial damage. Among these are PINK1 in the PINK1-Parkin mitophagy pathway and OMA1 and DELE1 in the mitochondrial integrated stress response (mt-ISR). These pathways are often activated together and have complementary functions. The PINK1-Parkin pathway eliminates damaged mitochondria. The mt-ISR adapts cellular metabolism – particularly protein metabolism – to the stress-state caused by mitochondrial dysfunction. We have recently been studying the coordination of these pathways in vivo, using models of mitochondrial myopathy caused by mitochondrial protein misfolding. These studies demonstrate the importance of these pathways for survival and also highlight key differences between the behavior of these pathways in cultured cells vs. post-mitotic tissue.