Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury.

Auotphagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury

MCOLN1 is a ROS sensor in lysosomes that regulates autophagy

Cellular stresses trigger autophagy to remove damaged macromolecules and organelles. Lysosomes 'host' multiple stress-sensing mechanisms that trigger the coordinated biogenesis of autophagosomes and lysosomes. For example, transcription factor (TF)EB, which regulates autophagy and lysosome biogenesis, is activated following the inhibition of mTOR, a lysosome-localized nutrient sensor. Here we s...

Lysosome calcium in ROS regulation of autophagy.

Lysosomes, the cell's recycling center, undergo nutrient-sensitive adaptive changes in function and biogenesis, i.e., lysosomal adaptation. We recently discovered that lysosomes also mediate the cell's "survival" response (i.e., autophagy) to oxidative stress through the activation of TFEB (transcription factor EB), a master regulator of lysosome biogenesis and autophagy. MCOLN1/TRPML1, the pri...

Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death.

Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyt...

Autophagy: the pathogenic agent in muscle damage

Recently autophagy has attracted considerable attention because of its role in a wide variety of diseases including neurodegenerative disorders, cancer, myopathies, and lysosomal storage diseases. Autophagy is a “self-eating” process that brings proteins and damaged organelles enclosed in double-membrane autophagosomes to lysosomes for digestion and recycling. Functional lysosomes are essential...