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  • Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway.

Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway.

Cell reports (2020-02-06)
Michael M Dubreuil, David W Morgens, Kanji Okumoto, Masanori Honsho, Kévin Contrepois, Brittany Lee-McMullen, Gavin McAllister Traber, Ria S Sood, Scott J Dixon, Michael P Snyder, Yukio Fujiki, Michael C Bassik
ABSTRACT

Reactive oxygen species (ROS) play critical roles in metabolism and disease, yet a comprehensive analysis of the cellular response to oxidative stress is lacking. To systematically identify regulators of oxidative stress, we conducted genome-wide Cas9/CRISPR and shRNA screens. This revealed a detailed picture of diverse pathways that control oxidative stress response, ranging from the TCA cycle and DNA repair machineries to iron transport, trafficking, and metabolism. Paradoxically, disrupting the pentose phosphate pathway (PPP) at the level of phosphogluconate dehydrogenase (PGD) protects cells against ROS. This dramatically alters metabolites in the PPP, consistent with rewiring of upper glycolysis to promote antioxidant production. In addition, disruption of peroxisomal import unexpectedly increases resistance to oxidative stress by altering the localization of catalase. Together, these studies provide insights into the roles of peroxisomal matrix import and the PPP in redox biology and represent a rich resource for understanding the cellular response to oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-PMP70 antibody, Mouse monoclonal, clone 70-18, purified from hybridoma cell culture
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, ACS reagent
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide phosphate sodium salt, pkg of 5 mg (per vial)