Cystathionine β-synthase regulates mitochondrial morphogenesis in ovarian cancer

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Prabir Kumar ChakrabortyPriyabrata Mukherjee

Abstract

Deregulation of mitochondrial morphogenesis, a dynamic equilibrium between mitochondrial fusion and fission processes, is now evolving as a key metabolic event that fuels tumor growth and therapy resistance. However, fundamental knowledge underpinning how cancer cells reprogram mitochondrial morphogenesis remains incomplete. Here, we report that cystathionine β-synthase (CBS) reprograms mitochondrial morphogenesis in ovarian cancer (OvCa) cells by selectively regulating the stability of mitofusin 2 (MFN2). Clinically, high expression of both CBS and MFN2 implicates poor overall survival of OvCa patients, and a significant association between CBS and MFN2 expression exists in individual patients in the same data set. The silencing of CBS by small interfering RNA or inhibition of its catalytic activity by a small molecule inhibitor creates oxidative stress that activates JNK. Activated JNK phosphorylates MFN2 to recruit homologous to the E6-AP carboxyl terminus' domain-containing ubiquitin E3 ligase for its degradation via the ubiquitin-proteasome system. Supplementation with hydrogen sulfide or glutathione (the catalytic products of CBS enzymatic activity), anti-oxidants, or a JNK inhibitor restores MFN2 expression. In CBS-silen...Continue Reading

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Citations

May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brennah MurphyPriyabrata Mukherjee
May 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Geeta RaoPriyabrata Mukherjee
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Aug 31, 2021·Frontiers in Cell and Developmental Biology·Sofia C NunesJacinta Serpa

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