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Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress by Ying Liu; Kejia Liu; Rick F. Thorne; Ronghua Shi; Qingyuan Zhang; Mian Wu; Lianxin Liu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress about?

Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex belonging to the mitochondrial respiratory chain and uniquely links the tricarboxylic acid (TCA) cycle with oxidative phosphorylation. Cancer-related SDH mutations promote succinate accumulation, which is regarded as an oncometabolite. Post-translational modifications of SDH complex components are known to regulate SDH activity, although the contribution of SUMOylation remains unclear. Here, we show that SDHA is SUMOylated by PIAS3 and deSUMOylated by SENP2, events dictating the assembly and activity of the SDH complex. Moreover, CBP acetylation of SENP2 negatively regulates its deSUMOylation activity. Under glutamine deprivation, CBP levels decrease, and the ensuing SENP2 activation and SDHA deSUMOylation serve to concurrently dampen the TCA cycle and electron transport chain (ETC) activity. Along with succinate accumulation, this mechanism avoids excessive reactive oxygen species (ROS) production to promote cancer cell survival. This study elucidates a major function of mitochondrial-localized SENP2 and expands our understanding of the role of SUMOylation in resolving metabolic stress.

Who reads Mitochondrial SENP2 regulates the assembly of SDH complex under metabolic stress?

Author

Ying Liu; Kejia Liu; Rick F. Thorne; Ronghua Shi; Qingyuan Zhang; Mian Wu; Lianxin Liu

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)