PMID- 35873543 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220726 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib. PG - 932116 LID - 10.3389/fphar.2022.932116 [doi] LID - 932116 AB - Mitochondria, as the powerhouse of cells, are involved in various processes of cellular homeostasis, especially energy metabolism. The morphology of mitochondria is a critical indicator for their functions, referring to mitochondrial fusion and fission. Here, we performed structured illumination microscopy (SIM) to measure the mitochondrial morphology in living cells. Benefitting from its nano-scale resolution, this SIM-based strategy can quantify the fusion and fission of mitochondria with high sensitivity. Furthermore, as type 2 diabetes mellitus (T2DM) is caused by a disorder of energy substrate utilization, this strategy has the potential to study T2DM by analyzing the mitochondrial morphology of insulin-resistant (IR) cells. With SIM, we found that mitochondrial fission was increased in IR MRC-5, LO2, FHs 74 Int, and HepG2 cells but not in IR Huh7 cells with high-invasiveness ability. Furthermore, we found that metformin could inhibit mitochondrial fission in IR cells, and sorafenib could promote mitochondrial fusion in HepG2 cancer cells, especially in those IR cells. To conclude, mitochondrial fission is involved in T2DM, and cancer cells with high-invasiveness ability may be equipped with stronger resistance to energy metabolism disorder. In addition, the pharmacodynamics of metformin and sorafenib in cancer may be related to the inhibition of mitochondrial fission, especially for patients with T2DM. CI - Copyright (c) 2022 Du, Zhu, Zeng, Mu and Liu. FAU - Du, Yang AU - Du Y AD - Cancer Center, State Key Laboratory of Biotherapy, Department of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Zhu, Ya-Juan AU - Zhu YJ AD - Cancer Center, State Key Laboratory of Biotherapy, Department of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Zeng, Bo AU - Zeng B AD - Dean's Office, West China Hospital, Sichuan University, Chengdu, China. FAU - Mu, Xiao-Li AU - Mu XL AD - Cancer Center, State Key Laboratory of Biotherapy, Department of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Liu, Ji-Yan AU - Liu JY AD - Cancer Center, State Key Laboratory of Biotherapy, Department of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. LA - eng PT - Journal Article DEP - 20220706 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9298863 OTO - NOTNLM OT - T2DM OT - metformin OT - mitochondria OT - sorafenib OT - structured illumination microscopy COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/26 06:00 MHDA- 2022/07/26 06:01 PMCR- 2022/07/06 CRDT- 2022/07/25 03:37 PHST- 2022/04/29 00:00 [received] PHST- 2022/06/07 00:00 [accepted] PHST- 2022/07/25 03:37 [entrez] PHST- 2022/07/26 06:00 [pubmed] PHST- 2022/07/26 06:01 [medline] PHST- 2022/07/06 00:00 [pmc-release] AID - 932116 [pii] AID - 10.3389/fphar.2022.932116 [doi] PST - epublish SO - Front Pharmacol. 2022 Jul 6;13:932116. doi: 10.3389/fphar.2022.932116. eCollection 2022.