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SUCLG2 Regulates Mitochondrial Dysfunction through Succinylation in Lung Adenocarcinoma
Qifan Hu1,2,3, Jing Xu2, Lei Wang2
1Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 31, 2023
Summary
Succinyl-coenzyme A (CoA) synthetase GDP-forming subunit β (SUCLG2) deletion impairs mitochondrial function in lung adenocarcinoma (LUAD). SUCLG2 succinylation enhances its stability, promoting LUAD cell proliferation and tumorigenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Mitochondrial dysfunction and altered energy metabolism are hallmarks of cancer.
- Mechanisms driving mitochondrial dysfunction in cancer progression remain incompletely understood.
Purpose of the Study:
- To investigate the role of succinyl-coenzyme A (CoA) synthetase GDP-forming subunit β (SUCLG2) in lung adenocarcinoma (LUAD) mitochondrial dysfunction.
- To elucidate the regulatory mechanisms of SUCLG2 stability and its impact on cancer progression.
Main Methods:
- Succinylome analysis to assess protein succinylation levels.
- Enzyme activity and protein stability assays.
- Investigation of protein-protein interactions and degradation pathways (ubiquitination, lysosomal degradation).
Main Results:
- SUCLG2 deletion increases mitochondrial protein succinylation, inhibiting metabolic enzyme function and dampening mitochondrial activity in LUAD.
- SUCLG2 succinylation at Lys93 enhances its stability, promoting LUAD cell proliferation and tumorigenesis.
- Sirtuin 5 (SIRT5) desuccinylates SUCLG2, leading to TRIM21-mediated ubiquitination and lysosomal degradation.
Conclusions:
- SUCLG2 plays a critical role in regulating mitochondrial function and homeostasis in LUAD.
- Succinylation-mediated regulation of SUCLG2 stability is a novel mechanism influencing LUAD progression.
- Targeting SUCLG2 offers a potential therapeutic strategy for LUAD treatment.
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