The Peroxisome-Autophagy Redox Connection: A Double-Edged Sword?
Hongli Li, Celien Lismont, Iulia Revenco, Mohamed A. F. Hussein, Cláudio F. Costa, Marc Fransen
Abstract
Peroxisomes harbor numerous enzymes that can produce or degrade hydrogen peroxide (H 2 O 2 ). Depending on its local concentration and environment, this oxidant can function as a redox signaling molecule or cause stochastic oxidative damage. Currently, it is well-accepted that dysfunctional peroxisomes are selectively removed by the autophagy-lysosome pathway. This process, known as “pexophagy,” may serve a protective role in curbing peroxisome-derived oxidative stress. Peroxisomes also have the intrinsic ability to mediate and modulate H 2 O 2 -driven processes, including (selective) autophagy. However, the molecular mechanisms underlying these phenomena are multifaceted and have only recently begun to receive the attention they deserve. This review provides a comprehensive overview of what is known about the bidirectional relationship between peroxisomal H 2 O 2 metabolism and (selective) autophagy. After introducing the general concepts of (selective) autophagy, we critically examine the emerging roles of H 2 O 2 as one of the key modulators of the lysosome-dependent catabolic program. In addition, we explore possible relationships among peroxisome functioning, cellular H 2 O 2 levels, and autophagic signaling in health and disease. Finally, we highlight the most important challenges that need to be tackled to understand how alterations in peroxisomal H 2 O 2 metabolism contribute to autophagy-related disorders.