Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Nov 12

PMID 33178694

Citations 52

Authors

Lin Ren

Xiaodan Chen

Xiaobing Chen

Jiayan Li

Bin Cheng

Juan Xia

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) are pivotal to tissue homeostasis, repair, and regeneration due to their potential for self-renewal, multilineage differentiation, and immune modulation. Mitochondria are highly dynamic organelles that maintain their morphology via continuous fission and fusion, also known as mitochondrial dynamics. MSCs undergo specific mitochondrial dynamics during proliferation, migration, differentiation, apoptosis, or aging. Emerging evidence suggests that mitochondrial dynamics are key contributors to stem cell fate determination. The coordination of mitochondrial fission and fusion is crucial for cellular function and stress responses, while abnormal fission and/or fusion causes MSC dysfunction. This review focuses on the role of mitochondrial dynamics in MSC commitment under physiological and stress conditions. We highlight mechanistic insights into modulating mitochondrial dynamics and mitochondrial strategies for stem cell-based regenerative medicine. These findings shed light on the contribution of mitochondrial dynamics to MSC fate and MSC-based tissue repair.

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References

Romero-Moya D, Bueno C, Montes R, Navarro-Montero O, Iborra F, Lopez L . Cord blood-derived CD34+ hematopoietic cells with low mitochondrial mass are enriched in hematopoietic repopulating stem cell function. Haematologica. 2013; 98(7):1022-9. PMC: 3696604. DOI: 10.3324/haematol.2012.079244. View

Carling D . The AMP-activated protein kinase cascade--a unifying system for energy control. Trends Biochem Sci. 2004; 29(1):18-24. DOI: 10.1016/j.tibs.2003.11.005. View

Marycz K, Houston J, Weiss C, Rocken M, Kornicka K . 5-Azacytidine and Resveratrol Enhance Chondrogenic Differentiation of Metabolic Syndrome-Derived Mesenchymal Stem Cells by Modulating Autophagy. Oxid Med Cell Longev. 2019; 2019:1523140. PMC: 6535830. DOI: 10.1155/2019/1523140. View

Hawkins K, Joy S, Delhove J, Kotiadis V, Fernandez E, FitzPatrick L . NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming. Cell Rep. 2016; 14(8):1883-91. PMC: 4785773. DOI: 10.1016/j.celrep.2016.02.003. View

Senos Demarco R, Uyemura B, DAlterio C, Jones D . Mitochondrial fusion regulates lipid homeostasis and stem cell maintenance in the Drosophila testis. Nat Cell Biol. 2019; 21(6):710-720. DOI: 10.1038/s41556-019-0332-3. View

Lang A, Anand R, Altinoluk-Hambuchen S, Ezzahoini H, Stefanski A, Iram A . SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy. Aging (Albany NY). 2017; 9(10):2163-2189. PMC: 5680561. DOI: 10.18632/aging.101307. View

Jheng H, Huang S, Kuo H, Hughes M, Tsai Y . Molecular insight and pharmacological approaches targeting mitochondrial dynamics in skeletal muscle during obesity. Ann N Y Acad Sci. 2015; 1350:82-94. DOI: 10.1111/nyas.12863. View

He H, Yu B, Liu Z, Ye G, You W, Hong Y . Vascular progenitor cell senescence in patients with Marfan syndrome. J Cell Mol Med. 2019; 23(6):4139-4152. PMC: 6533473. DOI: 10.1111/jcmm.14301. View

Disatnik M, Ferreira J, Campos J, Gomes K, Dourado P, Qi X . Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc. 2013; 2(5):e000461. PMC: 3835263. DOI: 10.1161/JAHA.113.000461. View

10.

Ikeda Y, Shirakabe A, Brady C, Zablocki D, Ohishi M, Sadoshima J . Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system. J Mol Cell Cardiol. 2014; 78:116-22. PMC: 4268018. DOI: 10.1016/j.yjmcc.2014.09.019. View

11.

Guo J, Ren R, Yao X, Ye Y, Sun K, Lin J . PKM2 suppresses osteogenesis and facilitates adipogenesis by regulating β-catenin signaling and mitochondrial fusion and fission. Aging (Albany NY). 2020; 12(4):3976-3992. PMC: 7066892. DOI: 10.18632/aging.102866. View

12.

Sisakhtnezhad S, Alimoradi E, Akrami H . External factors influencing mesenchymal stem cell fate in vitro. Eur J Cell Biol. 2016; 96(1):13-33. DOI: 10.1016/j.ejcb.2016.11.003. View

13.

Bianco P . "Mesenchymal" stem cells. Annu Rev Cell Dev Biol. 2014; 30:677-704. DOI: 10.1146/annurev-cellbio-100913-013132. View

14.

Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A . Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment. Int J Mol Sci. 2018; 19(2). PMC: 5855582. DOI: 10.3390/ijms19020360. View

15.

Fillmore N, Huqi A, Jaswal J, Mori J, Paulin R, Haromy A . Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival. PLoS One. 2015; 10(3):e0120257. PMC: 4358990. DOI: 10.1371/journal.pone.0120257. View

16.

Wu J, Zhang W, Ran Q, Xiang Y, Zhong J, Li S . The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis. Stem Cells Int. 2018; 2018:1540148. PMC: 5903338. DOI: 10.1155/2018/1540148. View

17.

Kang S, Haydar G, Taniane C, Farrell G, Arias I, Lippincott-Schwartz J . AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function. PLoS One. 2016; 11(10):e0165638. PMC: 5085033. DOI: 10.1371/journal.pone.0165638. View

18.

Folmes C, Nelson T, Martinez-Fernandez A, Arrell D, Lindor J, Dzeja P . Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 2011; 14(2):264-71. PMC: 3156138. DOI: 10.1016/j.cmet.2011.06.011. View

19.

Zhang H, Menzies K, Auwerx J . The role of mitochondria in stem cell fate and aging. Development. 2018; 145(8). PMC: 5964648. DOI: 10.1242/dev.143420. View

20.

Li C, Sun L, Pang C . Synergistic protection of N-acetylcysteine and ascorbic acid 2-phosphate on human mesenchymal stem cells against mitoptosis, necroptosis and apoptosis. Sci Rep. 2015; 5:9819. PMC: 4408980. DOI: 10.1038/srep09819. View