ETMM-06. ELEVATED MITOCHONDRIAL TOM20 EXPRESSION SUPPRESSES GLIOMA MALIGNANCY BY ENHANCING OXIDATIVE PHOSPHORYLATION. (25th March 2021)

• Record Type: Journal Article
• Authors: Li, Mao; Zhang, Shuxin; Yang, Wanchun; Yang, Yuan; Pang, Dejiang; Mao, Qing; Chen, Mina; Liu, Yanhui
• Is Part Of: Neuro-oncology advances. Volume 3(2021)Supplement 1
• Page Start: i15
• Page End: i15
• Publication Date: 2021-03-25
• Subjects: 616.99481
• DOI: 10.1093/noajnl/vdab024.062
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: BACKGROUND: Malignant glioma display a metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation (OXPHOs). However, the underlying mechanism for this metabolic switch in glioma is not well elucidated. Mitochondrial translocases of the outer/inner membrane (TOMs/TIMs) import proteins into mitochondria, and could thereby regulate OXPHOs. The objective of this study is to investigate the expression of TOM/TIM members in glioma, as well as their functional and therapeutic implications. METHODS: Transcriptome sequencing (RNA-seq), real-time PCR, Western blot, and immunohistochemistry were used to identify Tom20 as a significantly downregulated TOM/TIM protein in 20 paired glioma/Peritumoral tissues. To study the biological function of Tom20 in glioma, we interrogated metabolic alterations in Tom20 overexpressed glioma cells by GC-MS metabolomics, acetyl-CoA assay, and Seahorse assay. We compared the cell proliferation and viability profiles between Tom20 overexpressed and control cells in vitro and in vivo. To investigate the therapeutic implication of Tom20 expression, we tested OXPHOs inhibitor metformin in Tom20 overexpressed cells and xenograft mouse models. RESULTS: We find that Tom20, a critical component of the mitochondrial outer membrane translocases, is downregulated in malignant gliomas. Using an integrative approach spanning bioinformatic analysis, metabolomics, and functional approaches, we reveal that Tom20 elevation activates mitochondrial OXPHOs in glioma cells and reduces tumor malignancy. We also find that Tom20 upregulation sensitizes glioma cells to metformin in vitro, and improves the therapeutic efficacy of metformin in glioma in vivo. CONCLUSION: Our work defines Tom20 as a glioma suppressor and an indicator of metformin treatment in glioma.