Mitochondrial membrane potential-enriched CHO host: a novel and powerful tool for improving biomanufacturing capability

References

• Davies SL, Lovelady CS, Grainger RK, Racher AJ, Young RJ, James DC. Functional heterogeneity and heritability in CHO cell populations. Biotechnol Bioeng. 2013;110(1):260–16. doi:10.1002/bit.24621.
   PubMed Web of Science ®Google Scholar
• O’Callaghan PM, Berthelot ME, Young RJ, Graham JW, Racher AJ, Aldana D. Diversity in host clone performance within a Chinese hamster ovary cell line. Biotechnol Prog. 2015;31(5):1187–200. doi:10.1002/btpr.2097.
   PubMed Web of Science ®Google Scholar
• Cost GJ, Freyvert Y, Vafiadis A, Santiago Y, Miller JC, Rebar E, Collingwood TN, Snowden A, Gregory PD. BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. Biotechnol Bioeng. 2010;105(2):330–40. doi:10.1002/bit.22541.
   PubMed Web of Science ®Google Scholar
• Fussenegger M, Fassnacht D, Schwartz R, Zanghi JA, Graf M, Bailey JE, Pörtner R. Regulated overexpression of the survival factor bcl-2 in CHO cells increases viable cell density in batch culture and decreases DNA release in extended fixed-bed cultivation. Cytotechnology. 2000;32(1):45–61. doi:10.1023/A:1008168522385.
   PubMed Web of Science ®Google Scholar
• Majors BS, Betenbaugh MJ, Pederson NE, Chiang GG. Mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in Chinese hamster ovary cells. Biotechnol Prog. 2009;25(4):1161–68. doi:10.1002/btpr.192.
   PubMed Web of Science ®Google Scholar
• Misaghi S, Qu Y, Snowden A, Chang J, Snedecor B. Resilient immortals, characterizing and utilizing bax/bak deficient Chinese hamster ovary (CHO) cells for high titer antibody production. Biotechnol Prog. 2013;29(3):727–37. doi:10.1002/btpr.1722.
   PubMed Web of Science ®Google Scholar
• Gupta SK, Srivastava SK, Sharma A, Nalage VH, Salvi D, Kushwaha H, Chitnis NB, Shukla P. Metabolic engineering of CHO cells for the development of a robust protein production platform. PLoS One. 2017;12(8):e0181455. doi:10.1371/journal.pone.0181455.
   PubMed Web of Science ®Google Scholar
• Toussaint C, Henry O, Durocher Y. Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures. J Biotechnol. 2016;217:122–31. doi:10.1016/j.jbiotec.2015.11.010.
   PubMed Web of Science ®Google Scholar
• Dreesen IA, Fussenegger M. Ectopic expression of human mTOR increases viability, robustness, cell size, proliferation, and antibody production of Chinese hamster ovary cells. Biotechnol Bioeng. 2011;108(4):853–66. doi:10.1002/bit.22990.
   PubMed Web of Science ®Google Scholar
• Pybus LP, Dean G, West NR, Smith A, Daramola O, Field R, Wilkinson SJ, James DC. Model-directed engineering of “difficult-to-express” monoclonal antibody production by Chinese hamster ovary cells. Biotechnol Bioeng. 2014;111(2):372–85. doi:10.1002/bit.25116.
   PubMed Web of Science ®Google Scholar
• Le Fourn V, Girod PA, Buceta M, Regamey A, Mermod N. CHO cell engineering to prevent polypeptide aggregation and improve therapeutic protein secretion. Metab Eng. 2014;21:91–102. doi:10.1016/j.ymben.2012.12.003.
   PubMed Web of Science ®Google Scholar
• Peng RW, Abellan E, Fussenegger M. Differential effect of exocytic SNAREs on the production of recombinant proteins in mammalian cells. Biotechnol Bioeng. 2011;108(3):611–20. doi:10.1002/bit.22986.
   PubMed Web of Science ®Google Scholar
• Bort JA, Stern B, Borth N. CHO-K1 host cells adapted to growth in glutamine-free medium by FACS-assisted evolution. Biotechnol J. 2010;5(10):1090–97. doi:10.1002/biot.201000095.
   PubMed Web of Science ®Google Scholar
• Prentice HL, Ehrenfels BN, Sisk WP. Improving performance of mammalian cells in fed-batch processes through “bioreactor evolution”. Biotechnol Prog. 2007;23(2):458–64. doi:10.1021/bp060296y.
   PubMed Web of Science ®Google Scholar
• Sunley K, Tharmalingam T, Butler M. CHO cells adapted to hypothermic growth produce high yields of recombinant beta-interferon. Biotechnol Prog. 2008;24(4):898–906. doi:10.1002/btpr.9.
   PubMed Web of Science ®Google Scholar
• Weinguny M, Klanert G, Eisenhut P, Jonsson A, Ivansson D, Lövgren A, Borth N. Directed evolution approach to enhance efficiency and speed of outgrowth during single cell subcloning of Chinese hamster ovary cells. Comput Struct Biotechnol J. 2020;18:1320–29. doi:10.1016/j.csbj.2020.05.020.
   PubMed Web of Science ®Google Scholar
• Chandrawanshi V, Kulkarni R, Prabhu A, Mehra S. Enhancing titers and productivity of rCHO clones with a combination of an optimized fed-batch process and ER-stress adaptation. J Biotechnol. 2020;311:49–58. doi:10.1016/j.jbiotec.2020.02.008.
   PubMed Web of Science ®Google Scholar
• Mistry RK, Kelsall E, Sou SN, Barker H, Jenns M, Willis K, Zurlo F, Hatton D, Gibson SJ. A novel hydrogen peroxide evolved CHO host can improve the expression of difficult to express bispecific antibodies. Biotechnol Bioeng. 2021;(6). doi:10.1002/bit.27744.
   PubMed Web of Science ®Google Scholar
• Desalle R, Schierwater B, Hadrys H. MtDNA: the small workhorse of evolutionary studies. Front Biosci (Landmark Ed). 2017;22(5):873–87. doi:10.2741/4522.
   PubMedGoogle Scholar
• Dhiman H, Gerstl MP, Ruckerbauer D, Hanscho M, Himmelbauer H, Clarke C, Barron N, Zanghellini J, Borth N. Genetic and epigenetic variation across genes involved in energy metabolism and mitochondria of Chinese hamster ovary cell lines. Biotechnol J. 2019;14(7):e1800681. doi:10.1002/biot.201800681.
   PubMed Web of Science ®Google Scholar
• Chakrabarti L, Mathew A, Li L, Han S, Klover J, Albanetti T, Hawley-Nelson P. Mitochondrial membrane potential identifies cells with high recombinant protein productivity. J Immunol Methods. 2019;464:31–39. doi:10.1016/j.jim.2018.10.007.
   PubMed Web of Science ®Google Scholar
• Kelly PS, Clarke C, Costello A, Monger C, Meiller J, Dhiman H, Borth N, Betenbaugh MJ, Clynes M, Barron N. Ultra-deep next generation mitochondrial genome sequencing reveals widespread heteroplasmy in Chinese hamster ovary cells. Metab Eng. 2017;41:11–22. doi:10.1016/j.ymben.2017.02.001.
   PubMed Web of Science ®Google Scholar
• Mootha VK, Bunkenborg J, Olsen JV, Hjerrild M, Wisniewski JR, Stahl E, Bolouri MS, Ray HN, Sihag S, Kamal M, Patterson N, et al. Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell. 2003;115(5):629–40. doi:10.1016/s0092-8674(03)00926-7.
   PubMed Web of Science ®Google Scholar
• Wasilewski M, Chojnacka K, Chacinska A. Protein trafficking at the crossroads to mitochondria. Biochim Biophys Acta Mol Cell Res. 2017;1864(1):125–37. doi:10.1016/j.bbamcr.2016.10.019.
   PubMed Web of Science ®Google Scholar
• Nusinow DP, Szpyt J, Ghandi M, Rose CM, McDonald III ER, Kalocsay M, Jané-Valbuena J, Gelfand E, Schweppe DK, Jedrychowski M, Golji J, et al. Quantitative proteomics of the cancer cell line encyclopedia. Cell. 2020;180(2):387–402 e316. doi:10.1016/j.cell.2019.12.023.
   PubMed Web of Science ®Google Scholar
• Handlogten MW, Lee‐O’Brien A, Roy G, Levitskaya SV, Venkat R, Singh S, Ahuja S. Intracellular response to process optimization and impact on productivity and product aggregates for a high-titer CHO cell process. Biotechnol Bioeng. 2018;115(1):126–38. doi:10.1002/bit.26460.
   PubMed Web of Science ®Google Scholar
• Evans K, Albanetti T, Venkat R, Schoner R, Savery J, Miro‐Quesada G, Rajan B, Groves C. Assurance of monoclonality in one round of cloning through cell sorting for single cell deposition coupled with high resolution cell imaging. Biotechnol Prog. 2015;31(5):1172–78. doi:10.1002/btpr.2145.
   PubMed Web of Science ®Google Scholar
• Maftah A, Petit JM, Ratinaud MH, Julien R. 10-N nonyl-acridine orange: a fluorescent probe which stains mitochondria independently of their energetic state. Biochem Biophys Res Commun. 1989;164(1):185–90. doi:10.1016/0006-291X(89)91700-2.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay P, Rajesh M, Haskó G, Hawkins BJ, Madesh M, Pacher P. Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy. Nat Protoc. 2007;2(9):2295–301. doi:10.1038/nprot.2007.327.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, Stanger BZ, Chung I, Rhim AD, Di Magliano MP. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res. 2013;73(20):6359–74. doi:10.1158/0008-5472.CAN-13-1558-T.
   PubMed Web of Science ®Google Scholar
• Cazares LH, Chaerkady R, Samuel Weng SH, Boo CC, Cimbro R, Hsu HE, Rajan S, Dall’Acqua W, Clarke L, Ren K, McTamney P, et al. Development of a parallel reaction monitoring mass spectrometry assay for the detection of SARS-CoV-2 spike glycoprotein and nucleoprotein. Anal Chem. 2020;92(20):13813–21. doi:10.1021/acs.analchem.0c02288.
   PubMed Web of Science ®Google Scholar
• HaileMariam M, Eguez RV, Singh H, Bekele S, Ameni G, Pieper R, Yu Y. S-Trap, an ultrafast sample-preparation approach for shotgun proteomics. J Proteome Res. 2018;17(9):2917–24. doi:10.1021/acs.jproteome.8b00505.
   PubMed Web of Science ®Google Scholar
• Kalli A, Smith GT, Sweredoski MJ, Hess S. Evaluation and optimization of mass spectrometric settings during data-dependent acquisition mode: focus on LTQ-Orbitrap mass analyzers. J Proteome Res. 2013;12(7):3071–86. doi:10.1021/pr3011588.
   PubMed Web of Science ®Google Scholar
• Mao S, Chaerkady R, Yu W, D’Angelo G, Garcia A, Chen H, Barrett AM, Phipps S, Fleming R, Hess S, Koopmann JO, et al. Resistance to pyrrolobenzodiazepine dimers is associated with SLFN11 downregulation and can be reversed through inhibition of ATR. Mol Cancer Ther. 2021;20(3):541–52. doi:10.1158/1535-7163.MCT-20-0351.
   PubMed Web of Science ®Google Scholar
• Ritchie ME, Phipson B, Wu DI, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi:10.1093/nar/gkv007.
   PubMed Web of Science ®Google Scholar
• Hadley W. in ggplot2. Springer; 2016.
   Google Scholar
• Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, Friedberg I, Hamelryck T, Kauff F, Wilczynski B, De Hoon MJ, et al. Biopython: freely available python tools for computational molecular biology and bioinformatics. Bioinformatics. 2009;25(11):1422–23. doi:10.1093/bioinformatics/btp163.
   PubMed Web of Science ®Google Scholar
• Fabian PG, Varoquaux A, Gramfort V, Bertrand M, Al OGE. J Mach Learn Res. 2011;12: 2825–30. (ed Mikio Braun).
   Web of Science ®Google Scholar
• Pilbrough W, Munro TP, Gray P. Intraclonal protein expression heterogeneity in recombinant CHO cells. PLoS One. 2009;4(12):e8432. doi:10.1371/journal.pone.0008432.
   PubMed Web of Science ®Google Scholar
• Tharmalingam T, Barkhordarian H, Tejeda N, Daris K, Yaghmour S, Yam P, Lu F, Goudar C, Munro T, Stevens J. Characterization of phenotypic and genotypic diversity in subclones derived from a clonal cell line. Biotechnol Prog. 2018;34(3):613–23. doi:10.1002/btpr.2666.
   PubMed Web of Science ®Google Scholar
• Zagari F, Jordan M, Stettler M, Broly H, Wurm FM. Lactate metabolism shift in CHO cell culture: the role of mitochondrial oxidative activity. N Biotechnol. 2013;30(2):238–45. doi:10.1016/j.nbt.2012.05.021.
   PubMed Web of Science ®Google Scholar
• Wang B, Albanetti T, Miro‐Quesada G, Flack L, Li L, Klover J, Burson K, Evans K, Ivory W, Bowen M, Schoner R, et al. High-throughput screening of antibody-expressing CHO clones using an automated shaken deep-well system. Biotechnol Prog. 2018;34(6):1460–71. doi:10.1002/btpr.2721.
   PubMed Web of Science ®Google Scholar
• Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, Babenko VA, Zorov SD, Balakireva AV, Juhaszova M, Sollott SJ, et al. Mitochondrial membrane potential. Anal Biochem. 2018;552:50–59. doi:10.1016/j.ab.2017.07.009.
   PubMed Web of Science ®Google Scholar
• Li S, Cha SW, Heffner K, Hizal DB, Bowen MA, Chaerkady R, Cole RN, Tejwani V, Kaushik P, Henry M, Meleady P, et al. Proteogenomic annotation of Chinese hamsters reveals extensive novel translation events and endogenous retroviral elements. J Proteome Res. 2019;18(6):2433–45. doi:10.1021/acs.jproteome.8b00935.
   PubMed Web of Science ®Google Scholar
• Tyanova S, Temu T, Cox J. The maxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc. 2016;11(12):2301–19. doi:10.1038/nprot.2016.136.
   PubMed Web of Science ®Google Scholar
• Daumke O, Roux A. Mitochondrial homeostasis: how do dimers of mitofusins mediate mitochondrial fusion? Curr Biol. 2017;27(9):R353–R356. doi:10.1016/j.cub.2017.03.024.
   PubMed Web of Science ®Google Scholar
• Franco A, Kitsis RN, Fleischer JA, Gavathiotis E, Kornfeld OS, Gong G, Biris N, Benz A, Qvit N, Donnelly SK, Chen Y, et al. Correcting mitochondrial fusion by manipulating mitofusin conformations. Nature. 2016;540(7631):74–79. doi:10.1038/nature20156.
   PubMed Web of Science ®Google Scholar
• Basso V, Marchesan E, Peggion C, Chakraborty J, von Stockum S, Giacomello M, Ottolini D, Debattisti V, Caicci F, Tasca E, Pegoraro V, et al. Regulation of ER-mitochondria contacts by parkin via Mfn2. Pharmacol Res. 2018;138:43–56. doi:10.1016/j.phrs.2018.09.006.
   PubMed Web of Science ®Google Scholar
• de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008;456(7222):605–10. doi:10.1038/nature07534.
   PubMed Web of Science ®Google Scholar
• Naon D, Zaninello M, Giacomello M, Varanita T, Grespi F, Lakshminaranayan S, Serafini A, Semenzato M, Herkenne S, Hernández-Alvarez MI, Zorzano A, et al. Critical reappraisal confirms that mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proc Natl Acad Sci U S A. 2016;113(40):11249–54. doi:10.1073/pnas.1606786113.
   PubMed Web of Science ®Google Scholar
• Harper JW, Ordureau A, Heo JM. Building and decoding ubiquitin chains for mitophagy. Nat Rev Mol Cell Biol. 2018;19(2):93–108. doi:10.1038/nrm.2017.129.
   PubMed Web of Science ®Google Scholar
• Pfanner N, Warscheid B, Wiedemann N. Mitochondrial proteins: from biogenesis to functional networks. Nat Rev Mol Cell Biol. 2019;20(5):267–84. doi:10.1038/s41580-018-0092-0.
   PubMed Web of Science ®Google Scholar
• Pickles S, Vigie P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018;28(4):R170–R185. doi:10.1016/j.cub.2018.01.004.
   PubMed Web of Science ®Google Scholar
• Bhupana JN, Huang BT, Liou GG, Calkins MJ, Lin-Chao S. Gas7 knockout affects PINK1 expression and mitochondrial dynamics in mouse cortical neurons. FASEB Bioadv. 2020;2(3):166–81. doi:10.1096/fba.2019-00091.
   PubMedGoogle Scholar
• Munoz JP, Ivanova S, Sánchez‐Wandelmer J, Martínez‐Cristóbal P, Noguera E, Sancho A, Díaz‐Ramos A, Hernández‐Alvarez MI, Sebastián D, Mauvezin C, Palacín M, et al. Mfn2 modulates the UPR and mitochondrial function via repression of PERK. EMBO J. 2013;32(17):2348–61. doi:10.1038/emboj.2013.168.
   PubMed Web of Science ®Google Scholar
• Ngoh GA, Papanicolaou KN, Walsh K. Loss of mitofusin 2 promotes endoplasmic reticulum stress. J Biol Chem. 2012;287(24):20321–32. doi:10.1074/jbc.M112.359174.
   PubMed Web of Science ®Google Scholar
• Mracek T, Drahota Z, Houstek J. The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues. Biochim Biophys Acta. 2013;1827(3):401–10. doi:10.1016/j.bbabio.2012.11.014.
   PubMed Web of Science ®Google Scholar
• Birch JR, Racher AJ. Antibody production. Adv Drug Deliv Rev. 2006;58(5–6):671–85. doi:10.1016/j.addr.2005.12.006.
   PubMed Web of Science ®Google Scholar
• Cacciatore JJ, Chasin LA, Leonard EF. Gene amplification and vector engineering to achieve rapid and high-level therapeutic protein production using the Dhfr-based CHO cell selection system. Biotechnol Adv. 2010;28(6):673–81. doi:10.1016/j.biotechadv.2010.04.003.
   PubMed Web of Science ®Google Scholar
• Zhu J, Hatton D. New mammalian expression systems. Adv Biochem Eng Biotechnol. 2017. doi:10.1007/10_2016_55.
   Web of Science ®Google Scholar
• Kelley B. Developing therapeutic monoclonal antibodies at pandemic pace. Nat Biotechnol. 2020;38(5):540–45. doi:10.1038/s41587-020-0512-5.
   PubMed Web of Science ®Google Scholar
• Bolisetty P, Tremml G, Xu S, Khetan A. Enabling speed to clinic for monoclonal antibody programs using a pool of clones for IND-enabling toxicity studies. MAbs. 2020;12(1):1763727. doi:10.1080/19420862.2020.1763727.
   PubMed Web of Science ®Google Scholar
• Fan L, Rizzi G, Bierilo K, Tian J, Yee JC, Russell R, Das TK. Comparative study of therapeutic antibody candidates derived from mini-pool and clonal cell lines. Biotechnol Prog. 2017;33(6):1456–62. doi:10.1002/btpr.2477.
   PubMed Web of Science ®Google Scholar
• Munro TP, Le K, Le H, Zhang L, Stevens J, Soice N, Benchaar SA, Hong RW, Goudar CT. Accelerating patient access to novel biologics using stable pool-derived product for non-clinical studies and single clone-derived product for clinical studies. Biotechnol Prog. 2017;33(6):1476–82. doi:10.1002/btpr.2572.
   PubMed Web of Science ®Google Scholar
• Kadenbach B. Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim Biophys Acta. 2003;1604(2):77–94. doi:10.1016/S0005-2728(03)00027-6.
   PubMed Web of Science ®Google Scholar
• Chen LB. Mitochondrial membrane potential in living cells. Annu Rev Cell Biol. 1988;4(1):155–81. doi:10.1146/annurev.cb.04.110188.001103.
   PubMedGoogle Scholar
• Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20(7):745–54. doi:10.1038/s41556-018-0124-1.
   PubMed Web of Science ®Google Scholar
• Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a parkin receptor for culling damaged mitochondria. Science. 2013;340(6131):471–75. doi:10.1126/science.1231031.
   PubMed Web of Science ®Google Scholar
• Durcan TM, Fon EA. The three ‘P’s of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 2015;29:989–99. doi:10.1101/gad.262758.115.
   PubMed Web of Science ®Google Scholar
• McLelland GL, Goiran T, Yi W, Dorval G, Chen CX, Lauinger ND, Krahn AI, Valimehr S, Rakovic A, Rouiller I, Durcan TM, et al. Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. Elife. 2018;7. doi:10.7554/eLife.32866.
   PubMed Web of Science ®Google Scholar
• Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem. 2003;278(19):17190–97. doi:10.1074/jbc.M212754200.
   PubMed Web of Science ®Google Scholar
• Chen H, Chomyn A, Chan DC. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem. 2005;280(28):26185–92. doi:10.1074/jbc.M503062200.
   PubMed Web of Science ®Google Scholar
• Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG, et al. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol. 2015;208(4):429–42. doi:10.1083/jcb.201411100.
   PubMed Web of Science ®Google Scholar
• Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacín M, Zorzano A. The Charcot-Marie-tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 2005;14(11):1405–15. doi:10.1093/hmg/ddi149.
   PubMed Web of Science ®Google Scholar
• Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998;280:1763–66. doi:10.1126/science.280.5370.1763.
   PubMed Web of Science ®Google Scholar
• Szabadkai G, Bianchi K, Várnai P, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Balla T, Rizzuto R. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol. 2006;175(6):901–11. doi:10.1083/jcb.200608073.
   PubMed Web of Science ®Google Scholar
• Debattisti V, Pendin D, Ziviani E, Daga A, Scorrano L. Reduction of endoplasmic reticulum stress attenuates the defects caused by drosophila mitofusin depletion. J Cell Biol. 2014;204(3):303–12. doi:10.1083/jcb.201306121.
   PubMed Web of Science ®Google Scholar
• Sebastian D, Hernández-Alvarez MI, Segalés J, Sorianello E, Muñoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P, Orešič M, et al. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci U S A. 2012;109(14):5523–28. doi:10.1073/pnas.1108220109.
   PubMed Web of Science ®Google Scholar
• Pecinova A, Alán L, Brázdová A, Vrbacký M, Pecina P, Drahota Z, Houštěk J, Mráček T. Role of mitochondrial glycerol-3-Phosphate dehydrogenase in metabolic adaptations of prostate cancer. Cells. 2020;9(8). doi:10.3390/cells9081764.
   Web of Science ®Google Scholar
• Thakur S, Daley B, Gaskins K, Vasko VV, Boufraqech M, Patel D, Sourbier C, Reece J, Cheng SY, Kebebew E, Agarwal S, et al. Metformin targets mitochondrial glycerophosphate dehydrogenase to control rate of oxidative phosphorylation and growth of thyroid cancer in vitro and in vivo. Clin Cancer Res. 2018;24(16):4030–43. doi:10.1158/1078-0432.CCR-17-3167.
   PubMed Web of Science ®Google Scholar