Rescue of Dysfunctional Autophagy

Cystic Fibrosis Cells Attenuates Hyperinflammatory Responses Rescue of Dysfunctional Autophagy

Preparing the Membrane for Autophagosome Biogenesis

Autophagy is a fundamental strategy eukaryotic cells employ for bulk turnover of cytoplasmic components to maintain cellular homeostasis. At the organismal level, autophagy is involved in a variety of physiological processes such as development, metabolism and immunity. Dysfunctional autophagy has been implicated in numerous human disorders including cancer, neurodegeneration, aging, infection ...

Inhibition of mTOR reduces lipotoxic cell death in primary macrophages through an autophagy-independent mechanism.

Macrophage dysfunction in obesity and diabetes is associated with persistent inflammation and poor wound healing responses. Relevant to these phenotypes, we have previously shown that macrophage activation in a high-fat environment results in cell death via a mechanism that involves lysosome damage. While searching for signaling pathways that were required for this response, we discovered that ...

ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy.

Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 inter...

Inhibition of autophagy induction delays neuronal cell loss caused by dysfunctional ESCRT-III in frontotemporal dementia.

Autophagy is a conserved lysosomal protein degradation pathway whose precise roles in age-dependent neurodegenerative diseases remain largely unknown. Here we show that the autophagy inhibitor 3-methyladenine delays neuronal cell loss caused by dysfunctional endosomal sorting complex required for transport III (ESCRT-III), either through loss of its essential component mSnf7-2 or ectopic expres...