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Autophagy. 2016 Oct 2;12(10):1954-1955. Epub 2016 Aug 2.

Lysosome calcium in ROS regulation of autophagy.

Author information

1
a Department of Molecular, Cellular, and Developmental Biology , University of Michigan , Ann Arbor , MI , USA.

Abstract

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 principal Ca2+ release channel on the lysosomal membrane, serves as the redox sensor in this process. Increasing reactive oxygen species (ROS) levels, either endogenously by mitochondrial damage or exogenously, directly activates MCOLN1 to induce lysosomal Ca2+ release, triggering PPP3/calcineurin-dependent TFEB nuclear translocation to enhance autophagy. Hence, ROS may induce autophagy by activating the MCOLN1-lysosome Ca2+-TFEB pathway, facilitating the removal of damaged mitochondria and excess ROS. Our findings have revealed a lysosomal signaling mechanism for cells to respond to oxidative bursts and adapt to oxidative stress.

KEYWORDS:

ROS; TFEB; TRPML1; autophagy; lysosomal Ca2+; lysosome; lysosome biogenesis; mitophagy

PMID:
27485905
PMCID:
PMC5079666
DOI:
10.1080/15548627.2016.1212787
[Indexed for MEDLINE]
Free PMC Article

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