Mitochondrial DNA and Exercise: Implications for Health and Injuries in Sports

Recently, several studies have highlighted the tight connection between mitochondria and physical activity. Mitochondrial functions are important in high-demanding metabolic activities, such as endurance sports. Moreover, regular training positively affects metabolic health by increasing mitochondrial oxidative capacity and regulating glucose metabolism. Exercise could have multiple effects, also on the mitochondrial DNA (mtDNA) and vice versa; some studies have investigated how mtDNA polymorphisms can affect the performance of general athletes and mtDNA haplogroups seem to be related to the performance of elite endurance athletes. Along with several stimuli, including pathogens, stress, trauma, and reactive oxygen species, acute and intense exercise also seem to be responsible for mtDNA release into the cytoplasm and extracellular space, leading to the activation of the innate immune response. In addition, several sports are characterized by a higher frequency of injuries, including cranial trauma, associated with neurological consequences. However, with regular exercise, circulating cell-free mtDNA levels are kept low, perhaps promoting cf-mtDNA removal, acting as a protective factor against inflammation.

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Faculty Opinions recommendation of Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12101966.13250065 ◽

2011 ◽

Author(s):

Michael McDermott ◽

Michael Sprakes

Keyword(s):

Mitochondrial Dna ◽

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Nalp3 Inflammasome

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Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

Genetics and Molecular Biology ◽

10.1590/s1415-47572013000300005 ◽

2013 ◽

Vol 36 (3) ◽

pp. 329-335 ◽

Cited By ~ 7

Author(s):

Juan J. Yunis ◽

Emilio J. Yunis

Keyword(s):

Mitochondrial Dna ◽

Mtdna Haplogroups

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The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes

Cells ◽

10.3390/cells9020512 ◽

2020 ◽

Vol 9 (2) ◽

pp. 512 ◽

Cited By ~ 8

Author(s):

Calina Betlazar ◽

Ryan J. Middleton ◽

Richard Banati ◽

Guo-Jun Liu

Keyword(s):

Paradigm Shift ◽

Inflammatory Responses ◽

Innate Immune ◽

Translocator Protein ◽

Imaging Studies ◽

Immunomodulatory Effects ◽

Cellular Functions ◽

Mitochondrial Functions ◽

Cellular Bioenergetics ◽

Mitochondrial Membrane Protein

The translocator protein (TSPO) is an outer mitochondrial membrane protein that is widely used as a biomarker of neuroinflammation, being markedly upregulated in activated microglia in a range of brain pathologies. Despite its extensive use as a target in molecular imaging studies, the exact cellular functions of this protein remain in question. The long-held view that TSPO plays a fundamental role in the translocation of cholesterol through the mitochondrial membranes, and thus, steroidogenesis, has been disputed by several groups with the advent of TSPO knockout mouse models. Instead, much evidence is emerging that TSPO plays a fundamental role in cellular bioenergetics and associated mitochondrial functions, also part of a greater role in the innate immune processes of microglia. In this review, we examine the more direct experimental literature surrounding the immunomodulatory effects of TSPO. We also review studies which highlight a more central role for TSPO in mitochondrial processes, from energy metabolism, to the propagation of inflammatory responses through reactive oxygen species (ROS) modulation. In this way, we highlight a paradigm shift in approaches to TSPO functioning.

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Mitochondrial DNA: Distribution, Mutations, and Elimination

Cells ◽

10.3390/cells8040379 ◽

2019 ◽

Vol 8 (4) ◽

pp. 379 ◽

Cited By ~ 10

Author(s):

Yan ◽

Duanmu ◽

Zeng ◽

Liu ◽

Song

Keyword(s):

Mitochondrial Dna ◽

Mitochondrial Matrix ◽

Endonuclease G ◽

Respiratory Complexes ◽

Dna Distribution ◽

Mitochondrial Functions ◽

Mitochondrial Respiratory

Mitochondrion harbors its own DNA (mtDNA), which encodes many critical proteins for the assembly and activity of mitochondrial respiratory complexes. mtDNA is packed by many proteins to form a nucleoid that uniformly distributes within the mitochondrial matrix, which is essential for mitochondrial functions. Defects or mutations of mtDNA result in a range of diseases. Damaged mtDNA could be eliminated by mitophagy, and all paternal mtDNA are degraded by endonuclease G or mitophagy during fertilization. In this review, we describe the role and mechanism of mtDNA distribution and elimination. In particular, we focus on the regulation of paternal mtDNA elimination in the process of fertilization.

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Mitochondria and the success of somatic cell nuclear transfer cloning: from nuclear - mitochondrial interactions to mitochondrial complementation and mitochondrial DNA recombination

Reproduction Fertility and Development ◽

10.1071/rd04115 ◽

2005 ◽

Vol 17 (2) ◽

pp. 69 ◽

Cited By ~ 36

Author(s):

Stefan Hiendleder ◽

Valeri Zakhartchenko ◽

Eckhard Wolf

Keyword(s):

Mitochondrial Dna ◽

Somatic Cell ◽

Somatic Cell Nuclear Transfer ◽

Nuclear Transfer ◽

Dna Recombination ◽

Epigenetic Reprogramming ◽

Research Activities ◽

Mitochondrial Functions ◽

New Findings ◽

Mitochondrial Dna Recombination

The overall success of somatic cell nuclear transfer (SCNT) cloning is rather unsatisfactory, both in terms of efficacy and from an animal health and welfare point of view. Most research activities have concentrated on epigenetic reprogramming problems as one major cause of SCNT failure. The present review addresses the limited success of mammalian SCNT from yet another viewpoint, the mitochondrial perspective. Mitochondria have a broad range of critical functions in cellular energy supply, cell signalling and programmed cell death and, thus, affect embryonic and fetal development, suggesting that inadequate or perturbed mitochondrial functions may adversely affect SCNT success. A survey of perinatal clinical data from human subjects with deficient mitochondrial respiratory chain activity has revealed a plethora of phenotypes that have striking similarities with abnormalities commonly encountered in SCNT fetuses and offspring. We discuss the limited experimental data on nuclear–mitochondrial interaction effects in SCNT and explore the potential effects in the context of new findings about the biology of mitochondria. These include mitochondrial fusion/fission, mitochondrial complementation and mitochondrial DNA recombination, processes that are likely to be affected by and impact on SCNT cloning. Furthermore, we indicate pathways that could link epigenetic reprogramming and mitochondria effects in SCNT and address questions and perspectives for future research.

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Mitochondrial DNA Haplogroups and Breast Cancer Risk Factors in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Genes ◽

10.3390/genes9080395 ◽

2018 ◽

Vol 9 (8) ◽

pp. 395 ◽

Cited By ~ 4

Author(s):

Vivienne Riley ◽

A Mesut Erzurumluoglu ◽

Santiago Rodriguez ◽

Carolina Bonilla

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Mitochondrial Dna ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mtdna Haplogroups ◽

Cancer Risk Factors ◽

Parents And Children ◽

Breast Cancer Risk Factors ◽

Avon Longitudinal Study

The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Linear and logistic regression models adjusted for age, sex and population stratification principal components were evaluated. After correction for multiple testing we found no evidence of association of European mtDNA haplogroups with any of the breast cancer risk factors analysed. Mitochondrial DNA haplogroups are unlikely to underlie susceptibility to breast cancer that occurs via the risk factors examined in this study of a population of European ancestry.

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Mitochondrial DNA Can Function as an Endogenous Innate Immune Activator of Alloreactive T Cells.

Transplantation Journal ◽

10.1097/00007890-201407151-01029 ◽

2014 ◽

Vol 98 ◽

pp. 323

Author(s):

T. Brennan ◽

L. Lin ◽

V. Rendell ◽

X. Huang ◽

Y. Yang

Keyword(s):

T Cells ◽

Mitochondrial Dna ◽

Innate Immune ◽

Alloreactive T Cells

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Functional Interplay between Cristae Biogenesis, Mitochondrial Dynamics and Mitochondrial DNA Integrity

International Journal of Molecular Sciences ◽

10.3390/ijms20174311 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4311 ◽

Cited By ~ 13

Author(s):

Arun Kumar Kondadi ◽

Ruchika Anand ◽

Andreas S. Reichert

Keyword(s):

Mitochondrial Dna ◽

Unique Feature ◽

Mitochondrial Dynamics ◽

Human Diseases ◽

Dna Integrity ◽

Cellular Processes ◽

The Past ◽

Mitochondrial Structure ◽

Mitochondrial Functions ◽

Cellular Organelles

Mitochondria are vital cellular organelles involved in a plethora of cellular processes such as energy conversion, calcium homeostasis, heme biogenesis, regulation of apoptosis and ROS reactive oxygen species (ROS) production. Although they are frequently depicted as static bean-shaped structures, our view has markedly changed over the past few decades as many studies have revealed a remarkable dynamicity of mitochondrial shapes and sizes both at the cellular and intra-mitochondrial levels. Aberrant changes in mitochondrial dynamics and cristae structure are associated with ageing and numerous human diseases (e.g., cancer, diabetes, various neurodegenerative diseases, types of neuro- and myopathies). Another unique feature of mitochondria is that they harbor their own genome, the mitochondrial DNA (mtDNA). MtDNA exists in several hundreds to thousands of copies per cell and is arranged and packaged in the mitochondrial matrix in structures termed mt-nucleoids. Many human diseases are mechanistically linked to mitochondrial dysfunction and alteration of the number and/or the integrity of mtDNA. In particular, several recent studies identified remarkable and partly unexpected links between mitochondrial structure, fusion and fission dynamics, and mtDNA. In this review, we will provide an overview about these recent insights and aim to clarify how mitochondrial dynamics, cristae ultrastructure and mtDNA structure influence each other and determine mitochondrial functions.

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