Spinelli, J. B. & Haigis, M. C. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol. 20, 745â754 (2018).
Quintana-Cabrera, R. & Scorrano, L. Determinants and outcomes of mitochondrial dynamics. Mol. Cell 83, 857â876 (2023).
Schworer, S. et al. Proline biosynthesis is a vent for TGFβ-induced mitochondrial redox stress. EMBO J. 39, e103334 (2020).
Arnold, P. K. et al. A non-canonical tricarboxylic acid cycle underlies cellular identity. Nature 603, 477â481 (2022).
Linder, S. J. et al. Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells. Nat. Metab. 5, 2131â2147 (2023).
Zhu, J. et al. Mitochondrial NADP(H) generation is essential for proline biosynthesis. Science 372, 968â972 (2021).
Pilley, S. E. et al. Loss of attachment promotes proline accumulation and excretion in cancer cells. Sci. Adv. 9, eadh2023 (2023).
Lee, M. S. et al. Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer. Nature 616, 339â347 (2023).
Gohil, V. M. et al. Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis. Nat. Biotechnol. 28, 249â255 (2010).
Cai, X. et al. Lactate activates the mitochondrial electron transport chain independently of its metabolism. Mol. Cell 83, 3904â3920 (2023).
Titov, D. V. et al. Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science 352, 231â235 (2016).
Yang, Z. et al. Pyrroline-5-carboxylate synthase senses cellular stress and modulates metabolism by regulating mitochondrial respiration. Cell Death Differ. 28, 303â319 (2021).
Zhang, B. et al. The proline synthesis enzyme P5CS forms cytoophidia in Drosophila. J. Genet. Genomics 47, 131â143 (2020).
Zhong, J. et al. Structural basis of dynamic P5CS filaments. eLife 11, e76107 (2022).
Chen, W. W., Freinkman, E., Wang, T., Birsoy, K. & Sabatini, D. M. Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism. Cell 166, 1324â1337 (2016).
Edwards-Hicks, J. et al. MYC sensitises cells to apoptosis by driving energetic demand. Nat. Commun. 13, 4674 (2022).
Fischer-Zirnsak, B. et al. Recurrent de novo mutations affecting residue Arg138 of pyrroline-5-carboxylate synthase cause a progeroid form of autosomal-dominant cutis laxa. Am. J. Hum. Genet. 97, 483â492 (2015).
Kamphorst, J. J. et al. Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein. Cancer Res. 75, 544â553 (2015).
Bartman, C. R. et al. Slow TCA flux and ATP production in primary solid tumours but not metastases. Nature 614, 349â357 (2023).
Collins, T. J., Berridge, M. J., Lipp, P. & Bootman, M. D. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 21, 1616â1627 (2002).
Benador, I. Y. et al. Mitochondria bound to lipid droplets have unique bioenergetics, composition, and dynamics that support lipid droplet expansion. Cell Metab. 27, 869â885 (2018).
Han, M. et al. Spatial mapping of mitochondrial networks and bioenergetics in lung cancer. Nature 615, 712â719 (2023).
Carraro, M. et al. The unique cysteine of F-ATP synthase OSCP subunit participates in modulation of the permeability transition pore. Cell Rep. 32, 108095 (2020).
Branon, T. C. et al. Efficient proximity labeling in living cells and organisms with TurboID. Nat. Biotechnol. 36, 880â887 (2018).
Luengo, A. et al. Increased demand for NAD+ relative to ATP drives aerobic glycolysis. Mol. Cell 81, 691â707 (2021).
Stephan, T. et al. MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO J. 39, e104105 (2020).
Quintana-Cabrera, R. et al. The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function. Nat. Commun. 9, 3399 (2018).
Cogliati, S. et al. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155, 160â171 (2013).
Detmer, S. A. & Chan, D. C. Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J. Cell Biol. 176, 405â414 (2007).
Giacomello, M., Pyakurel, A., Glytsou, C. & Scorrano, L. The cell biology of mitochondrial membrane dynamics. Nat. Rev. Mol. Cell Biol. 21, 204â224 (2020).
Yao, C.-H. et al. Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation. eLife 8, e41351 (2019).
Yasuda, T., Ishihara, T., Ichimura, A. & Ishihara, N. Mitochondrial dynamics define muscle fiber type by modulating cellular metabolic pathways. Cell Rep. 42, 112434 (2023).
Hsu, K.-S. et al. Cancer cell survival depends on collagen uptake into tumor-associated stroma. Nat. Commun. 13, 7078 (2022).
Kleele, T. et al. Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature 593, 435â439 (2021).
Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 49, D1541âD1547 (2021).
Wei, M. C. et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727â730 (2001).
Osellame, L. D. et al. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J. Cell Sci. 129, 2170â2181 (2016).
Korobova, F., Gauvin, T. J. & Higgs, H. N. A role for myosin II in mammalian mitochondrial fission. Curr. Biol. 24, 409â414 (2014).
Adams, K. J. et al. Skyline for small molecules: a unifying software package for quantitative metabolomics. J. Proteome Res. 19, 1447â1458 (2020).
Heinrich, P. et al. Correcting for natural isotope abundance and tracer impurity in MS-, MS/MS- and high-resolution-multiple-tracer-data from stable isotope labeling experiments with IsoCorrectoR. Sci. Rep. 8, 17910 (2018).
Chen, W. W., Freinkman, E. & Sabatini, D. M. Rapid immunopurification of mitochondria for metabolite profiling and absolute quantification of matrix metabolites. Nat. Protoc. 12, 2215â2231 (2017).
Cho, K. F. et al. Proximity labeling in mammalian cells with TurboID and split-TurboID. Nat. Protoc. 15, 3971â3999 (2020).
Vander Heiden, M. G., Chandel, N. S., Williamson, E. K., Schumacker, P. T. & Thompson, C. B. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, 627â637 (1997).