Autophagy in Disease and Therapy

Local ROS and inefficient autophagosome formation limit Optineurin-mediated mitophagy in neurons

In rat hippocampal neurons under mild oxidative stress, Optineurin-marked damaged mitochondria are engulfed slowly and reach lysosomes over days; scavenging mitochondrial reactive oxygen species or nutrient deprivation speeds this.

Novel reporter of the PINK1-Parkin mitophagy pathway identifies its damage sensor in the import gate

A HaloTagged MFN2 reporter enabled CRISPRi screens showing diverse mitochondrial damage activates PINK1-Parkin via membrane potential loss, with TOM retaining PINK1 when TIM23 is blocked.

In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment

Cryo-ET of Parkin-expressing U2OS cells shows oligomycin/antimycin depolarization moves some ATP synthase to the inner boundary membrane, abolishes matrix calcium granules, and favors closed prohibitin domes.