Genetic Impairment of Succinate Metabolism Disrupts Bioenergetic Sensing in Adrenal Neuroendocrine Cancer

Authors

Priyanka Gupta
Keehn Strange
Rahul Telange
Ailan Guo
Heather Hatch
Amin Sobh
Jonathan Elie
Angela M Carter
John Totenhagen
Chunfeng Tan
Yogesh A Sonawane
Jiri Neuzil
Amarnath Natarajan
Ashley J Ovens
Jonathan S Oakhill
Thorsten Wiederhold
Karel Pacak
Hans K Ghayee
Laurent Meijer
Sushanth Reddy
James A Bibb

Publication Date

8-16-2022

Journal

Cell Reports

Abstract

Metabolic dysfunction mutations can impair energy sensing and cause cancer. Loss of function of the mitochondrial tricarboxylic acid (TCA) cycle enzyme subunit succinate dehydrogenase B (SDHB) results in various forms of cancer typified by pheochromocytoma (PC). Here we delineate a signaling cascade where the loss of SDHB induces the Warburg effect, triggers dysregulation of [Ca

Keywords

Adenylate Kinase, Animals, Carcinoma, Neuroendocrine, Cyclin-Dependent Kinase 5, Energy Metabolism, Glycogen Synthase Kinase 3, Mice, Phosphorylation, Succinates, AMPK, CP: Cancer, CP: Metabolism, Cdk5, PRKAG2, SDHB, Warburg effect, cancer bioenergetics, neuroendocrine tumor, p53, pheochromocytoma, senescence

DOI

10.1016/j.celrep.2022.111218

PMID

35977518

PMCID

PMC9822535

PubMedCentral® Posted Date

1-6-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes