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Biology
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Mitochondrial Heterogeneity
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Mitochondrial Heterogeneity

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Biochemistry and Molecular Biology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 25499

Special Issue Editors

Dr. Amy Vincent

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Guest Editor
Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, 4th Floor Cookson Building, Frammlington Place, NE2 4HH, UK
Interests: mitochondria; skeletal muscle; mitochondrial disease; mitochondrial genetics; electron microscopy
Prof. Robert Lightowlers

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Guest Editor
Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, 4th Floor Cookson Building, Frammlington Place, NE2 4HH, UK
Interests: mitochondria; mitochondrial disease

Special Issue Information

Dear Colleagues,

As technological advances provided us unprecedented insight into biological processes at a sub-cellular and suborganeller level, there is a growing appreciation for the heterogeneity of the mitochondrial reticulum within individual cells. Within cells mitochondria in different subcellular locations are now known to be functionally and structurally specialised for their localised cellular roles. Contact with other organelles such as the endoplasmic reticulum marks the site of mitochondrial DNA replication and calcium signalling is heterogeneous throughout the cell. Furthermore, this heterogeneity occurs at the organelle level with adjacent cristae showing stark functional variation. This special issue invites original research papers and reviews that cover all aspects of mitochondrial heterogeneity.

Dr. Amy Vincent
Prof. Robert Lightowlers
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mitochondrial reticulum
  • Metabolism
  • Oxidative phosphorylation
  • Mitochondrial morphology
  • Mitochondrial DNA
  • Subellular heterogeneity

Published Papers (5 papers)

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Research

Jump to: Review

10 pages, 3701 KiB  
Article
Mitochondrial Translation Occurs Preferentially in the Peri-Nuclear Mitochondrial Network of Cultured Human Cells
by Christin A. Albus, Rolando Berlinguer-Palmini, Caroline Hewison, Fiona McFarlane, Elisabeta-Ana Savu, Robert N. Lightowlers, Zofia M. Chrzanowska-Lightowlers and Matthew Zorkau
Biology 2021, 10(10), 1050; https://doi.org/10.3390/biology10101050 - 15 Oct 2021
Cited by 2 | Viewed by 2388
Abstract
Human mitochondria are highly dynamic organelles, fusing and budding to maintain reticular networks throughout many cell types. Although extending to the extremities of the cell, the majority of the network is concentrated around the nucleus in most of the commonly cultured cell lines. [...] Read more.
Human mitochondria are highly dynamic organelles, fusing and budding to maintain reticular networks throughout many cell types. Although extending to the extremities of the cell, the majority of the network is concentrated around the nucleus in most of the commonly cultured cell lines. This organelle harbours its own genome, mtDNA, with a different gene content to the nucleus, but the expression of which is critical for maintaining oxidative phosphorylation. Recent advances in click chemistry have allowed us to visualise sites of mitochondrial protein synthesis in intact cultured cells. We show that the majority of translation occurs in the peri-nuclear region of the network. Further analysis reveals that whilst there is a slight peri-nuclear enrichment in the levels of mitoribosomal protein and mitochondrial rRNA, it is not sufficient to explain this substantial heterogeneity in the distribution of translation. Finally, we also show that in contrast, a mitochondrial mRNA does not show such a distinct gradient in distribution. These data suggest that the relative lack of translation in the peripheral mitochondrial network is not due to an absence of mitoribosomes or an insufficient supply of the mt-mRNA transcripts. Full article
(This article belongs to the Special Issue Mitochondrial Heterogeneity)
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11 pages, 1930 KiB  
Article
Mitochondrial Protein Abundance Gradients Require the Distribution of Separated Mitochondria
by Franziska Bollmann, Jan-Niklas Dohrke, Christian A. Wurm, Daniel C. Jans and Stefan Jakobs
Biology 2021, 10(7), 572; https://doi.org/10.3390/biology10070572 - 23 Jun 2021
Cited by 2 | Viewed by 2947
Abstract
Mitochondria are highly dynamic organelles that interchange their contents mediated by fission and fusion. However, it has previously been shown that the mitochondria of cultured human epithelial cells exhibit a gradient in the relative abundance of several proteins, with the perinuclear mitochondria generally [...] Read more.
Mitochondria are highly dynamic organelles that interchange their contents mediated by fission and fusion. However, it has previously been shown that the mitochondria of cultured human epithelial cells exhibit a gradient in the relative abundance of several proteins, with the perinuclear mitochondria generally exhibiting a higher protein abundance than the peripheral mitochondria. The molecular mechanisms that are required for the establishment and the maintenance of such inner-cellular mitochondrial protein abundance gradients are unknown. We verified the existence of inner-cellular gradients in the abundance of clusters of the mitochondrial outer membrane protein Tom20 in the mitochondria of kidney epithelial cells from an African green monkey (Vero cells) using STED nanoscopy and confocal microscopy. We found that the Tom20 gradients are established immediately after cell division and require the presence of microtubules. Furthermore, the gradients are abrogated in hyperfused mitochondrial networks. Our results suggest that inner-cellular protein abundance gradients from the perinuclear to the peripheral mitochondria are established by the trafficking of individual mitochondria to their respective cellular destination. Full article
(This article belongs to the Special Issue Mitochondrial Heterogeneity)
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Review

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25 pages, 5187 KiB  
Review
Mitochondrial Heterogeneity in Metabolic Diseases
by Jennifer Ngo, Corey Osto, Frankie Villalobos and Orian S. Shirihai
Biology 2021, 10(9), 927; https://doi.org/10.3390/biology10090927 - 17 Sep 2021
Cited by 12 | Viewed by 5297
Abstract
Mitochondria have distinct architectural features and biochemical functions consistent with cell-specific bioenergetic needs. However, as imaging and isolation techniques advance, heterogeneity amongst mitochondria has been observed to occur within the same cell. Moreover, mitochondrial heterogeneity is associated with functional differences in metabolic signaling, [...] Read more.
Mitochondria have distinct architectural features and biochemical functions consistent with cell-specific bioenergetic needs. However, as imaging and isolation techniques advance, heterogeneity amongst mitochondria has been observed to occur within the same cell. Moreover, mitochondrial heterogeneity is associated with functional differences in metabolic signaling, fuel utilization, and triglyceride synthesis. These phenotypic associations suggest that mitochondrial subpopulations and heterogeneity influence the risk of metabolic diseases. This review examines the current literature regarding mitochondrial heterogeneity in the pancreatic beta-cell and renal proximal tubules as they exist in the pathological and physiological states; specifically, pathological states of glucolipotoxicity, progression of type 2 diabetes, and kidney diseases. Emphasis will be placed on the benefits of balancing mitochondrial heterogeneity and how the disruption of balancing heterogeneity leads to impaired tissue function and disease onset. Full article
(This article belongs to the Special Issue Mitochondrial Heterogeneity)
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17 pages, 2333 KiB  
Review
Emerging Roles of the MICOS Complex in Cristae Dynamics and Biogenesis
by Ruchika Anand, Andreas S. Reichert and Arun Kumar Kondadi
Biology 2021, 10(7), 600; https://doi.org/10.3390/biology10070600 - 29 Jun 2021
Cited by 27 | Viewed by 8830
Abstract
Mitochondria are double membrane-enclosed organelles performing important cellular and metabolic functions such as ATP generation, heme biogenesis, apoptosis, ROS production and calcium buffering. The mitochondrial inner membrane (IM) is folded into cristae membranes (CMs) of variable shapes using molecular players including the ‘mitochondrial [...] Read more.
Mitochondria are double membrane-enclosed organelles performing important cellular and metabolic functions such as ATP generation, heme biogenesis, apoptosis, ROS production and calcium buffering. The mitochondrial inner membrane (IM) is folded into cristae membranes (CMs) of variable shapes using molecular players including the ‘mitochondrial contact site and cristae organizing system’ (MICOS) complex, the dynamin-like GTPase OPA1, the F1FO ATP synthase and cardiolipin. Aberrant cristae structures are associated with different disorders such as diabetes, neurodegeneration, cancer and hepato-encephalopathy. In this review, we provide an updated view on cristae biogenesis by focusing on novel roles of the MICOS complex in cristae dynamics and shaping of cristae. For over seven decades, cristae were considered as static structures. It was recently shown that cristae constantly undergo rapid dynamic remodeling events. Several studies have re-oriented our perception on the dynamic internal ambience of mitochondrial compartments. In addition, we discuss the recent literature which sheds light on the still poorly understood aspect of cristae biogenesis, focusing on the role of MICOS and its subunits. Overall, we provide an integrated and updated view on the relation between the biogenesis of cristae and the novel aspect of cristae dynamics. Full article
(This article belongs to the Special Issue Mitochondrial Heterogeneity)
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20 pages, 1482 KiB  
Review
Discovering Cellular Mitochondrial Heteroplasmy Heterogeneity with Single Cell RNA and ATAC Sequencing
by Aidan S. Marshall and Nick S. Jones
Biology 2021, 10(6), 503; https://doi.org/10.3390/biology10060503 - 5 Jun 2021
Cited by 5 | Viewed by 5027
Abstract
Next-generation sequencing technologies have revolutionised the study of biological systems by enabling the examination of a broad range of tissues. Its application to single-cell genomics has generated a dynamic and evolving field with a vast amount of research highlighting heterogeneity in transcriptional, genetic [...] Read more.
Next-generation sequencing technologies have revolutionised the study of biological systems by enabling the examination of a broad range of tissues. Its application to single-cell genomics has generated a dynamic and evolving field with a vast amount of research highlighting heterogeneity in transcriptional, genetic and epigenomic state between cells. However, compared to these aspects of cellular heterogeneity, relatively little has been gleaned from single-cell datasets regarding cellular mitochondrial heterogeneity. Single-cell sequencing techniques can provide coverage of the mitochondrial genome which allows researchers to probe heteroplasmies at the level of the single cell, and observe interactions with cellular function. In this review, we give an overview of two popular single-cell modalities—single-cell RNA sequencing and single-cell ATAC sequencing—whose throughput and widespread usage offers researchers the chance to probe heteroplasmy combined with cell state in detailed resolution across thousands of cells. After summarising these technologies in the context of mitochondrial research, we give an overview of recent methods which have used these approaches for discovering mitochondrial heterogeneity. We conclude by highlighting current limitations of these approaches and open problems for future consideration. Full article
(This article belongs to the Special Issue Mitochondrial Heterogeneity)
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