OGDH mediates the inhibition of SIRT5 on cell proliferation and migration of gastric cancer

Lu, Xin; Yang, Pengfei; Zhao, Xiaomin; Jiang, Mingzu; Hu, Sijun; Ouyang, Yanan; Zeng, Li; Wu, Jing

doi:10.1016/j.yexcr.2019.06.028

Cited by 32 publications

(29 citation statements)

References 46 publications

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“…However, in other cancers, such as liver cancer, SIRT5 expression was found to significantly decreased. 31 Whether SIRT5 acts as a tumor suppressor was unclear until a recent report by Lu et al 32 demonstrated that oxoglutarate dehydrogenase mediates the inhibitory effects of SIRT5 on the proliferation and migration of GC cells. In this study, we examined the expression of SIRT5 in GC patient specimens and found that tumor tissues had lower SIRT5 expression than normal tissues.…”

Section: Discussionmentioning

confidence: 99%

SIRT5 regulates autophagy and apoptosis in gastric cancer cells

Qian

et al. 2021

J Int Med Res

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Objective Accumulating evidence illustrates that sirtuins (SIRTs) regulate autophagy and apoptosis in cancer cells; however, the role of SIRT5 in gastric cancer (GC) cells remains unknown. In this study, we examined the role of SIRT5 in GC cells. Methods We detected SIRT5 protein levels in freshly collected samples from patients with GC. Next, we studied the function of SIRT5 in autophagy. Furthermore, the signaling pathway through which SIRT5 enhanced autophagy in GC cells was detected. In addition, we established a GC cell apoptosis model to analyze the role of SIRT5 in apoptosis. Results SIRT5 expression was downregulated in GC tissues. We discovered that SIRT5 promoted autophagy in GC cells. We demonstrated that SIRT5 enhanced autophagy in GC cells via the AMP-activated protein kinase–mammalian target of rapamycin signaling pathway. In addition, SIRT5 was degraded during apoptosis in GC cells. Meanwhile, we observed that calpains and caspase-related proteins were associated with SIRT5-related GC cell apoptosis. Conclusions SIRT5 is a crucial regulator of autophagy and apoptosis in GC cell lines that can maintain the balance of autophagy and apoptosis.

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Section: Discussionmentioning

confidence: 99%

SIRT5 regulates autophagy and apoptosis in gastric cancer cells

Qian

et al. 2021

J Int Med Res

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“…In contrast to SIRT4, SIRT5 expression was also decreased in normal cells while overexpression of SIRT5 inhibited cell growth by negatively regulating cyclin dependent kinase 2 (CDK2) and inhibiting the aerobic glycolytic capacity leading to the arrest of the G1/S phase of cell cycle in cancer cells [138]. Moreover, when overexpressed SIRT5 also desuccinylated oxoglutarate dehydrogenase (OGDH) and inhibited it leading to a decrease in mitochondrial membrane potential and ATP generation while increasing ROS levels in gastric cancer cells [139].…”

Section: Gastric Cancermentioning

confidence: 99%

Mitochondrial sirtuins in stem cells and cancer

Jaiswal

Zhu

et al. 2021

The FEBS Journal

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“…Two mitochondrial genes OGDH and LIAS (encoding lipoic acid synthase) were identified that are involved in the mechanism of regulation in hypoxia-inducible transcription factors (HIFs) under aerobic conditions [17]. Lu et al suggested that OGDHc mediates SIRT5 (sirtuin 5, an NAD + -dependent protein deacylase) function, a potential suppressor of cell growth and migration in gastric cancer [18]. The direct interaction between SIRT5 and OGDHc was shown and it was reported that desuccinylation of OGDHc by SIRT5 inhibits OGDHc activity [18].…”

Section: Introductionmentioning

confidence: 99%

“…Lu et al suggested that OGDHc mediates SIRT5 (sirtuin 5, an NAD + -dependent protein deacylase) function, a potential suppressor of cell growth and migration in gastric cancer [18]. The direct interaction between SIRT5 and OGDHc was shown and it was reported that desuccinylation of OGDHc by SIRT5 inhibits OGDHc activity [18]. The authors suggested that SIRT5 suppressed gastric cancer cell growth and migration by inhibiting mitochondrial function and by increasing ROS production via down-regulation of OGDHc activity.…”

Section: Introductionmentioning

confidence: 99%

Toward an Understanding Of the Structural and Mechanistic Aspects of Protein-Protein Interactions in 2-Oxo Acid Dehydrogenase Complexes

Nemeria¹,

Zhang²,

Leandro³

et al. 2021

Preprint

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The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

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OGDH mediates the inhibition of SIRT5 on cell proliferation and migration of gastric cancer

Cited by 32 publications

References 46 publications

SIRT5 regulates autophagy and apoptosis in gastric cancer cells

SIRT5 regulates autophagy and apoptosis in gastric cancer cells

Mitochondrial sirtuins in stem cells and cancer

Toward an Understanding Of the Structural and Mechanistic Aspects of Protein-Protein Interactions in 2-Oxo Acid Dehydrogenase Complexes

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