AUTHOR=Li Hongli , Lismont Celien , Revenco Iulia , Hussein Mohamed A. F. , Costa Cláudio F. , Fransen Marc 

TITLE=The Peroxisome-Autophagy Redox Connection: A Double-Edged Sword?

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.814047

DOI=10.3389/fcell.2021.814047

ISSN=2296-634X

ABSTRACT=<p>Peroxisomes harbor numerous enzymes that can produce or degrade hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). 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<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub> metabolism and (selective) autophagy. After introducing the general concepts of (selective) autophagy, we critically examine the emerging roles of H<sub>2</sub>O<sub>2</sub> as one of the key modulators of the lysosome-dependent catabolic program. In addition, we explore possible relationships among peroxisome functioning, cellular H<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> metabolism contribute to autophagy-related disorders.</p>