Mitochondria in Disease: Changes in Shapes and Dynamics

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2024 Feb 24

PMID 38402097

Authors

Brenita C Jenkins

Kit Neikirk

Prasanna Katti

Steven M Claypool

Annet Kirabo

Melanie R McReynolds

Antentor Hinton Jr

Affiliations

Soon will be listed here.

Abstract

Mitochondrial structure often determines the function of these highly dynamic, multifunctional, eukaryotic organelles, which are essential for maintaining cellular health. The dynamic nature of mitochondria is apparent in descriptions of different mitochondrial shapes [e.g., donuts, megamitochondria (MGs), and nanotunnels] and crista dynamics. This review explores the significance of dynamic alterations in mitochondrial morphology and regulators of mitochondrial and cristae shape. We focus on studies across tissue types and also describe new microscopy techniques for detecting mitochondrial morphologies both in vivo and in vitro that can improve understanding of mitochondrial structure. We highlight the potential therapeutic benefits of regulating mitochondrial morphology and discuss prospective avenues to restore mitochondrial bioenergetics to manage diseases related to mitochondrial dysfunction.

Citing Articles

Mitochondrial dysfunction is a hallmark of woody breast myopathy in broiler chickens.

Greene E, Chen P, Walk C, Bedford M, Dridi S Front Physiol. 2025; 16:1543788.

PMID: 40034536 PMC: 11872917. DOI: 10.3389/fphys.2025.1543788.

VDAC1: A Key Player in the Mitochondrial Landscape of Neurodegeneration.

Argueti-Ostrovsky S, Barel S, Kahn J, Israelson A Biomolecules. 2025; 15(1).

PMID: 39858428 PMC: 11762377. DOI: 10.3390/biom15010033.

N-lactoyl phenylalanine suppresses appetite and obesity with important implications for aging and age-related diseases.

Hinton Jr A, Neikirk K, Le H, Oliver A, Harris C, Martin P Aging Adv. 2025; 1(2):172-173.

PMID: 39845129 PMC: 11752169. DOI: 10.4103/agingadv.agingadv-d-24-00011.

Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications.

Hinton Jr A, Neikirk K, Le H, Harris C, Oliver A, Martin P Aging Adv. 2025; 1(2):154-171.

PMID: 39839811 PMC: 11748122. DOI: 10.4103/agingadv.agingadv-d-24-00012.

Protective Effects of Mdivi-1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization.

Hong C, Wang L, Zhou X, Zou L, Xiang X, Deng H CNS Neurosci Ther. 2025; 31(1):e70149.

PMID: 39791542 PMC: 11719124. DOI: 10.1111/cns.70149.

References

Kory N, de Bos J, van der Rijt S, Jankovic N, Gura M, Arp N . MCART1/SLC25A51 is required for mitochondrial NAD transport. Sci Adv. 2020; 6(43). PMC: 7577609. DOI: 10.1126/sciadv.abe5310. View

Qin J, Guo Y, Xue B, Shi P, Chen Y, Su Q . ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation. Nat Commun. 2020; 11(1):4471. PMC: 7478960. DOI: 10.1038/s41467-020-18202-4. View

Picca A, Guerra F, Calvani R, Bucci C, Lo Monaco M, Bentivoglio A . Mitochondrial Dysfunction and Aging: Insights from the Analysis of Extracellular Vesicles. Int J Mol Sci. 2019; 20(4). PMC: 6412692. DOI: 10.3390/ijms20040805. View

Anand R, Wai T, Baker M, Kladt N, Schauss A, Rugarli E . The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol. 2014; 204(6):919-29. PMC: 3998800. DOI: 10.1083/jcb.201308006. View

Cogliati S, Frezza C, Soriano M, Varanita T, Quintana-Cabrera R, Corrado M . Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell. 2013; 155(1):160-71. PMC: 3790458. DOI: 10.1016/j.cell.2013.08.032. View

Li H, Ruan Y, Zhang K, Jian F, Hu C, Miao L . Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization. Cell Death Differ. 2015; 23(3):380-92. PMC: 5072434. DOI: 10.1038/cdd.2015.102. View

Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko G, Rudka T . OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006; 126(1):177-89. DOI: 10.1016/j.cell.2006.06.025. View

RUSKA E . Nobel lecture. The development of the electron microscope and of electron microscopy. Biosci Rep. 1987; 7(8):607-29. DOI: 10.1007/BF01127674. View

Lejri I, Grimm A, Eckert A . Mitochondria, Estrogen and Female Brain Aging. Front Aging Neurosci. 2018; 10:124. PMC: 5934418. DOI: 10.3389/fnagi.2018.00124. View

10.

Liu X, Hajnoczky G . Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ. 2011; 18(10):1561-72. PMC: 3172112. DOI: 10.1038/cdd.2011.13. View

11.

Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek A, Spelbrink J . Composition and dynamics of human mitochondrial nucleoids. Mol Biol Cell. 2003; 14(4):1583-96. PMC: 153124. DOI: 10.1091/mbc.e02-07-0399. View

12.

Ahmad T, Aggarwal K, Pattnaik B, Mukherjee S, Sethi T, Tiwari B . Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death Dis. 2013; 4:e461. PMC: 3564000. DOI: 10.1038/cddis.2012.213. View

13.

Suh J, Kim N, Shim W, Lee S, Kim H, Moon E . Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis. Cell Metab. 2023; 35(2):345-360.e7. DOI: 10.1016/j.cmet.2023.01.003. View

14.

Ilamathi H, Ouellet M, Sabouny R, Desrochers-Goyette J, Lines M, Pfeffer G . A new automated tool to quantify nucleoid distribution within mitochondrial networks. Sci Rep. 2021; 11(1):22755. PMC: 8610998. DOI: 10.1038/s41598-021-01987-9. View

15.

Marshall A, Neikirk K, Stephens D, Vang L, Vue Z, Beasley H . Serial Block Face-Scanning Electron Microscopy as a Burgeoning Technology. Adv Biol (Weinh). 2023; 7(8):e2300139. PMC: 10950369. DOI: 10.1002/adbi.202300139. View

16.

Westrate L, Drocco J, Martin K, Hlavacek W, MacKeigan J . Mitochondrial morphological features are associated with fission and fusion events. PLoS One. 2014; 9(4):e95265. PMC: 3986258. DOI: 10.1371/journal.pone.0095265. View

17.

Schaum N, Lehallier B, Hahn O, Palovics R, Hosseinzadeh S, Lee S . Ageing hallmarks exhibit organ-specific temporal signatures. Nature. 2020; 583(7817):596-602. PMC: 7757734. DOI: 10.1038/s41586-020-2499-y. View

18.

Lawrie A, Rizzuto R, Pozzan T, Simpson A . A role for calcium influx in the regulation of mitochondrial calcium in endothelial cells. J Biol Chem. 1996; 271(18):10753-9. DOI: 10.1074/jbc.271.18.10753. View

19.

Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M . Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A. 2013; 110(15):5887-92. PMC: 3625323. DOI: 10.1073/pnas.1217823110. View

20.

Bron C, Gremillet P, Launay D, Jourlin M, Gautschi H, Bachi T . Three-dimensional electron microscopy of entire cells. J Microsc. 1990; 157(Pt 1):115-26. DOI: 10.1111/j.1365-2818.1990.tb02952.x. View