Mitochondrial Dynamics Regulates Drosophila Intestinal Stem Cell Differentiation

Overview

Journal Cell Death Discov

Date 2018 Aug 1

PMID 30062062

Citations 19

Authors

Hansong Deng

Shigeo Takashima

Manash Paul

Ming Guo

Volker Hartenstein

Affiliations

Soon will be listed here.

Abstract

Differentiation of stem/progenitor cells is associated with a substantial increase in mitochondrial mass and complexity. Mitochondrial dynamics, including the processes of fusion and fission, plays an important role for somatic cell reprogramming and pluripotency maintenance in induced pluripotent cells (iPSCs). However, the role of mitochondrial dynamics during stem/progenitor cell differentiation in vivo remains elusive. Here we found differentiation of Drosophila intestinal stem cell is accompanied with continuous mitochondrial fusion. Mitochondrial fusion defective(RNAi) ISCs contain less mitochondrial membrane potential, reduced ATP, and increased ROS level. Surprisingly, suppressing fusion also resulted in the failure of progenitor cells to differentiate. Cells did not switch on the expression of differentiation markers, and instead continued to show characteristics of progenitor cells. Meanwhile, proliferation or apoptosis was unaffected. The differentiation defect could be rescued by concomitant inhibition of Drp1, a mitochondrial fission molecule. Moreover, ROS scavenger also partially rescues opa1RNAi-associated differentiation defects via down-regulating JNK activity. We propose that mitochondrial fusion plays a pivotal role in controlling the developmental switch of stem cell fate.

Citing Articles

Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis.

Luo D, Zou M, Rao X, Wei M, Zhang L, Hua Y Poult Sci. 2025; 104(2):104754.

PMID: 39764876 PMC: 11760324. DOI: 10.1016/j.psj.2024.104754.

c-Jun N-terminal kinase signaling in aging.

Li Y, You L, Nepovimova E, Adam V, Heger Z, Jomova K Front Aging Neurosci. 2024; 16:1453710.

PMID: 39267721 PMC: 11390425. DOI: 10.3389/fnagi.2024.1453710.

Mitochondrial morphology dynamics and ROS regulate apical polarity and differentiation in Drosophila follicle cells.

Uttekar B, Verma R, Tomer D, Rikhy R Development. 2024; 151(5).

PMID: 38345270 PMC: 7616099. DOI: 10.1242/dev.201732.

Intestinal epithelial adaptations to vertical sleeve gastrectomy defined at single-cell resolution.

Koch-Laskowski K, Kim K, Bethea M, Fuller K, Sandoval D, Sethupathy P Genomics. 2024; 116(2):110805.

PMID: 38309446 PMC: 10959023. DOI: 10.1016/j.ygeno.2024.110805.

Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate.

Zhang C, Meng Y, Han J Cell Mol Life Sci. 2024; 81(1):26.

PMID: 38212548 PMC: 11072137. DOI: 10.1007/s00018-023-05070-6.

References

Aghajanian P, Takashima S, Paul M, Younossi-Hartenstein A, Hartenstein V . Metamorphosis of the Drosophila visceral musculature and its role in intestinal morphogenesis and stem cell formation. Dev Biol. 2016; 420(1):43-59. PMC: 5140094. DOI: 10.1016/j.ydbio.2016.10.011. View

Wang L, Zhang T, Wang L, Cai Y, Zhong X, He X . Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission. EMBO J. 2017; 36(10):1330-1347. PMC: 5430220. DOI: 10.15252/embj.201695417. View

Xiang G, Yang L, Long Q, Chen K, Tang H, Wu Y . BNIP3L-dependent mitophagy accounts for mitochondrial clearance during 3 factors-induced somatic cell reprogramming. Autophagy. 2017; 13(9):1543-1555. PMC: 5612220. DOI: 10.1080/15548627.2017.1338545. View

Poole A, Thomas R, Andrews L, McBride H, Whitworth A, Pallanck L . The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008; 105(5):1638-43. PMC: 2234197. DOI: 10.1073/pnas.0709336105. View

Takashima S, Mkrtchyan M, Younossi-Hartenstein A, Merriam J, Hartenstein V . The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling. Nature. 2008; 454(7204):651-5. DOI: 10.1038/nature07156. View

Johansen K, Green R, Iwaki D, Hernandez J, Lengyel J . The Drm-Bowl-Lin relief-of-repression hierarchy controls fore- and hindgut patterning and morphogenesis. Mech Dev. 2003; 120(10):1139-51. DOI: 10.1016/j.mod.2003.08.001. View

Cerveny K, Tamura Y, Zhang Z, Jensen R, Sesaki H . Regulation of mitochondrial fusion and division. Trends Cell Biol. 2007; 17(11):563-9. DOI: 10.1016/j.tcb.2007.08.006. View

Chen H, Vermulst M, Wang Y, Chomyn A, Prolla T, McCaffery J . Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010; 141(2):280-9. PMC: 2876819. DOI: 10.1016/j.cell.2010.02.026. View

Mathur D, Bost A, Driver I, Ohlstein B . A transient niche regulates the specification of Drosophila intestinal stem cells. Science. 2010; 327(5962):210-3. PMC: 2857772. DOI: 10.1126/science.1181958. View

10.

Paul M, Bisht B, Darmawan D, Chiou R, Ha V, Wallace W . Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling. Cell Stem Cell. 2014; 15(2):199-214. PMC: 4127166. DOI: 10.1016/j.stem.2014.05.009. View

11.

McQuibban G, Lee J, Zheng L, Juusola M, Freeman M . Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. Curr Biol. 2006; 16(10):982-9. DOI: 10.1016/j.cub.2006.03.062. View

12.

Hernandez-Garcia D, Wood C, Castro-Obregon S, Covarrubias L . Reactive oxygen species: A radical role in development?. Free Radic Biol Med. 2010; 49(2):130-43. DOI: 10.1016/j.freeradbiomed.2010.03.020. View

13.

Bach E, Ekas L, Ayala-Camargo A, Flaherty M, Lee H, Perrimon N . GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns. 2006; 7(3):323-31. DOI: 10.1016/j.modgep.2006.08.003. View

14.

Schieke S, Ma M, Cao L, McCoy Jr J, Liu C, Hensel N . Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells. J Biol Chem. 2008; 283(42):28506-12. PMC: 2568919. DOI: 10.1074/jbc.M802763200. View

15.

Hom J, Quintanilla R, Hoffman D, Bentley K, Molkentin J, Sheu S . The permeability transition pore controls cardiac mitochondrial maturation and myocyte differentiation. Dev Cell. 2011; 21(3):469-78. PMC: 3175092. DOI: 10.1016/j.devcel.2011.08.008. View

16.

Dimroth P, Kaim G, Matthey U . Crucial role of the membrane potential for ATP synthesis by F(1)F(o) ATP synthases. J Exp Biol. 1999; 203(Pt 1):51-9. DOI: 10.1242/jeb.203.1.51. View

17.

Szabadkai G, Simoni A, Bianchi K, De Stefani D, Leo S, Wieckowski M . Mitochondrial dynamics and Ca2+ signaling. Biochim Biophys Acta. 2006; 1763(5-6):442-9. DOI: 10.1016/j.bbamcr.2006.04.002. View

18.

Dai D, Danoviz M, Wiczer B, Laflamme M, Tian R . Mitochondrial Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes. Stem Cells Int. 2017; 2017:5153625. PMC: 5380852. DOI: 10.1155/2017/5153625. View

19.

Prieto J, Leon M, Ponsoda X, Garcia-Garcia F, Bort R, Serna E . Dysfunctional mitochondrial fission impairs cell reprogramming. Cell Cycle. 2016; 15(23):3240-3250. PMC: 5176137. DOI: 10.1080/15384101.2016.1241930. View

20.

Deng H, Gerencser A, Jasper H . Signal integration by Ca(2+) regulates intestinal stem-cell activity. Nature. 2015; 528(7581):212-7. PMC: 4669953. DOI: 10.1038/nature16170. View