Glutamine metabolic stress induces SLC25A6-dependent mitofission via MIC60–MIC19 complex disassembly in colorectal cancer

De Martino M, Rathmell JC, Galluzzi L, Vanpouille-Box C. Cancer cell metabolism and antitumour immunity. Nat Rev Immunol. 2024;24:654–69.

Google Scholar 

Stegen S, van Gastel N, Eelen G, Ghesquière B, D’Anna F, Thienpont B, et al. HIF-1α promotes glutamine-mediated redox homeostasis and glycogen-dependent bioenergetics to support postimplantation bone cell survival. Cell Metab. 2016;23:265–79.

Google Scholar 

Zhang G-F, Jensen MV, Gray SM, El K, Wang Y, Lu D, et al. Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion. Cell Metab. 2020;33:804–817.e5.

Google Scholar 

Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2021;21:141–62.

Google Scholar 

Vagaggini C, D’Ursi P, Poggialini F, Fossa P, Francesconi V, Trombetti G, et al. Deciphering the landscape of allosteric glutaminase 1 inhibitors as anticancer agents. Bioorg Chem. 2025;161:108523.

Google Scholar 

Vyas S, Zaganjor E, Haigis MC. Mitochondria and cancer. Cell. 2016;166:555–66.

Google Scholar 

Zong W-X, Rabinowitz JD, White E. Mitochondria and cancer. Mol Cell. 2016;61:667–76.

Google Scholar 

Sessions DT, Kashatus DF. Mitochondrial dynamics in cancer stem cells. Cell Mol Life Sci. 2021;78:3803–16.

Google Scholar 

Kasahara A, Scorrano L. Mitochondria: from cell death executioners to regulators of cell differentiation. Trends Cell Biol. 2014;24:761–70.

Google Scholar 

Bonora M, Giorgi C, Pinton P. Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 2022;23:266–85.

Google Scholar 

Waseem M, Wang B-D. Promising strategy of mptp modulation in cancer therapy: an emerging progress and future insight. In J Mol Sci. 2023;24:5564.

Bauer TM, Murphy E. Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circulation Res. 2020;126:280–93.

Google Scholar 

Bernardi P, Gerle C, Halestrap AP, Jonas EA, Karch J, Mnatsakanyan N, et al. Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell Death Differ. 2023;30:1869–85.

Google Scholar 

Zhang J, Wang X, Cui W, Wang W, Zhang H, Liu L, et al. Visualization of caspase-3-like activity in cells using a genetically encoded fluorescent biosensor activated by protein cleavage. Nat Commun. 2013;4:2157.

Google Scholar 

Li M, Thorne RF, Shi R, Zhang XD, Li J, Li J, et al. DDIT3 directs a dual mechanism to balance glycolysis and oxidative phosphorylation during glutamine deprivation. Adv Sci. 2021;8. e2003732.

Google Scholar 

Xu Z, Huang X, Su Q, Wang Q, Liu L, Shen Y, et al. Flemiphilippinin A induces paraptosis in lung cancer cells via c-Myc-driven endoplasmic reticulum stress and CHOP-mediated mitochondrial dysfunction. Phytomedicine. 2025;146:157098.

Google Scholar 

Li H, Ruan Y, Zhang K, Jian F, Hu C, Miao L, et al. Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization. Cell Death Differ. 2016;23:380–92.

Google Scholar 

Tsai PI, Papakyrikos AM, Hsieh CH, Wang X. Drosophila MIC60/mitofilin conducts dual roles in mitochondrial motility and crista structure. Mol Biol Cell. 2017;28:3471–9.

Google Scholar 

Stephan T, Bruser C, Deckers M, Steyer AM, Balzarotti F, Barbot M, et al. MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO J. 2020;39:e104105.

Google Scholar 

Tang J, Zhang K, Dong J, Yan C, Hu C, Ji H, et al. Sam50-Mic19-Mic60 axis determines mitochondrial cristae architecture by mediating mitochondrial outer and inner membrane contact. Cell Death Differ. 2020;27:146–60.

Google Scholar 

Benaroya H. Mitochondria and MICOS – function and modeling. Rev Neurosci. 2024;35:503–31.

Google Scholar 

Brenner C, Subramaniam K, Pertuiset C, Pervaiz S. Adenine nucleotide translocase family: four isoforms for apoptosis modulation in cancer. Oncogene. 2010;30:883–95.

Google Scholar 

Yang Z, Cheng W, Hong L, Chen W, Wang Y, Lin S, et al. Adenine nucleotide (ADP/ATP) translocase 3 participates in the tumor necrosis factor–induced apoptosis of MCF-7 cells. Mol Biol Cell. 2007;18:4681–9.

Google Scholar 

Ruprecht JJ, King MS, Zögg T, Aleksandrova AA, Pardon E, Crichton PG, et al. The molecular mechanism of transport by the mitochondrial ADP/ATP carrier. Cell. 2019;176:435–47.e15.

Google Scholar 

Hoshino A, Wang W-j, Wada S, McDermott-Roe C, Evans CS, Gosis B, et al. The ADP/ATP translocase drives mitophagy independent of nucleotide exchange. Nature. 2019;575:375–9.

Google Scholar 

Zhao L, Deng X, Li Y, Hu J, Xie L, Shi F, et al. Conformational change of adenine nucleotide translocase-1 mediates cisplatin resistance induced by EBV-LMP1. EMBO Mol Med. 2021;13:e14072.

Google Scholar 

Brustovetsky N. The Role of adenine nucleotide translocase in the mitochondrial permeability transition. Cells. 2020;9:2686.

Google Scholar 

Sprenger H-G, Langer T. The good and the bad of mitochondrial breakups. Trends Cell Biol. 2019;29:888–900.

Google Scholar 

Cai W-F, Zhang C, Wu Y-Q, Zhuang G, Ye Z, Zhang C-S, et al. Glutaminase GLS1 senses glutamine availability in a non-enzymatic manner triggering mitochondrial fusion. Cell Res. 2018;28:865–7.

Google Scholar 

Prasad P, Ghosh S, Roy SS. Glutamine deficiency promotes stemness and chemoresistance in tumor cells through DRP1-induced mitochondrial fragmentation. Cell Mol Life Sci. 2021;78:4821–45.

Google Scholar