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Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib

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 mic...

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Autores principales: Du, Yang, Zhu, Ya-Juan, Zeng, Bo, Mu, Xiao-Li, Liu, Ji-Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298863/
https://www.ncbi.nlm.nih.gov/pubmed/35873543
http://dx.doi.org/10.3389/fphar.2022.932116
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author Du, Yang
Zhu, Ya-Juan
Zeng, Bo
Mu, Xiao-Li
Liu, Ji-Yan
author_facet Du, Yang
Zhu, Ya-Juan
Zeng, Bo
Mu, Xiao-Li
Liu, Ji-Yan
author_sort Du, Yang
collection PubMed
description 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.
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spelling pubmed-92988632022-07-21 Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib Du, Yang Zhu, Ya-Juan Zeng, Bo Mu, Xiao-Li Liu, Ji-Yan Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-07-06 /pmc/articles/PMC9298863/ /pubmed/35873543 http://dx.doi.org/10.3389/fphar.2022.932116 Text en Copyright © 2022 Du, Zhu, Zeng, Mu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Du, Yang
Zhu, Ya-Juan
Zeng, Bo
Mu, Xiao-Li
Liu, Ji-Yan
Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title_full Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title_fullStr Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title_full_unstemmed Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title_short Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib
title_sort super-resolution quantification of t2dm-induced mitochondrial morphology changes and their implications in pharmacodynamics of metformin and sorafenib
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298863/
https://www.ncbi.nlm.nih.gov/pubmed/35873543
http://dx.doi.org/10.3389/fphar.2022.932116
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