NOX4 regulates autophagy during energy deprivation.
NADPH oxidase is a cellular enzyme devoted to the production of reactive oxygen species (ROS). NOX4 and NOX2 are the main isoforms of NADPH oxidase in the cardiovascular system. In our recent study, we demonstrated that NOX4, but not NOX2, is a critical mediator of the cardiomyocyte adaptive response to energy stress. NOX4 activity and protein levels are increased in the endoplasmic reticulum (ER) but not in mitochondria of cardiomyocytes during the early phase of energy deprivation. NOX4-derived production of ROS in the ER is a critical event that activates autophagy through stimulation of the EIF2AK3/PERK-EIF2S1/eIF-2α-ATF4 pathway. NOX4-dependent autophagy is an important mechanism to preserve cellular energy and limit cell death in energy-deprived cardiomyocytes. Aside from elucidating a crucial physiological function of NOX4 during cellular energy stress, our study dissects a novel signaling mechanism that regulates autophagy under this condition.
Cardiovascular Research Institute; Department of Cell Biology and Molecular Medicine; Rutgers New Jersey Medical School; Newark, NJ USA; IRCCS Neuromed; Pozzilli (IS), Italy.
Sebastiano
S
Sciarretta
IRCCS Neuromed; Pozzilli (IS), Italy; Department of Clinical and Molecular Medicine; School of Medicine and Psicology; University "Sapienza"; Rome, Italy.
Massimo
M
Volpe
Cardiovascular Research Institute; Department of Cell Biology and Molecular Medicine; Rutgers New Jersey Medical School; Newark, NJ USA.
Junichi
J
Sadoshima
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D015852:Eukaryotic Initiation Factor-2; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
Nox4; PERK; autophagy; endoplasmic reticulum; glucose deprivation; oxidative stress