The role of mitochondria in the development of breast cancer

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There is a hypothesis that mitochondrial dysfunction and mutations in the mitochondrial genome may play an important role in the carcinogenesis; however, despite many years of research, this issue is still the subject of scientific discussion. The review reflects modern views on the role of mitochondria and the mitochondrial genome in the development of breast cancer. Sources were searched in Pubmed and eLIBRARY.RU databases for the past 10 years and in article references. Articles were selected that contained data from case-control studies of breast cancer and studies of cybrid cells.

The survey of experimental and association studies has shown that the mitochondrial genome determines the characteristics of cellular metabolism in human populations at the global (by macrohaplogroups L, M, N), landscape (by haplogroups), population (by subhaplogroups), and individual levels (by SNPs, insertions, deletions) and can determine predisposition to cancer. Single nucleotide substitutions, deletions, and mitochondrial DNA copy number decline are not specific for breast cancer. Nevertheless, mitochondria have been experimentally shown to be directly involved in the development of malignant neoplasms in experimental animals. It is likely that mitochondrial involvement in carcinogenesis is associated with mitochondrial dysfunction, in which nuclear-mitochondrial relationships are disrupted. On the other hand, mutations with too strong effect, i.e., completely disrupting mitochondrial function, lose their tumorigenic potential. Mutations, deletions and changes in mitochondrial DNA copy number are undoubtedly associated with the development of breast cancer, being one of the most important elements of a complex web of numerous interactions.

作者简介

Dmitrii Tikhonov

M. K. Ammosov North-Eastern Federal University

编辑信件的主要联系方式.
Email: tikhonov.dmitri@yandex.ru
ORCID iD: 0000-0003-3385-9471
SPIN 代码: 5271-4123

Dr. Sci. (Med.), Professor

俄罗斯联邦, 58 Belinskogo street, 677000 Yakutsk

Mikael Vinokurov

M. K. Ammosov North-Eastern Federal University

Email: mm.vinokurov@s-vfu.ru
ORCID iD: 0000-0002-1235-6560
SPIN 代码: 8895-6455

Dr. Sci. (Med.), Professor

俄罗斯联邦, 58 Belinskogo street, 677000 Yakutsk

Nadezhda Kipriyanova

M. K. Ammosov North-Eastern Federal University

Email: kiprinad2@mail.ru

Dr. Sci. (Med.)

俄罗斯联邦, 58 Belinskogo street, 677000 Yakutsk

Maria Golubenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: maria-golubenko@medgenetics.ru
ORCID iD: 0000-0002-7692-9954
SPIN 代码: 5117-3684

Cand. Sci. (Biol.)

俄罗斯联邦, Tomsk

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2. Fig. 1. The electron transport chain of the inner membrane of mitochondria (adapted from [3]). CI–CV — complexes I–V; H+ — ionized hydrogen; NADH — reduced form of nicotinamidveadenine dinucleotide; NAD+ — oxidized form of nicotinamide adenine dinucleotide; Cyto C — cytochrome C; H2O — water; ADP — adenosine diphosphate; Pi — inorganic phosphorus; ATP — adenosine triphosphate; –ΔΨm — redox potential.

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3. Fig. 2. Мap of the human mitochondrial genome [by 5–7]. HSP — heavy strand promoter; LSP — light strand promoter; control region — control region that controls the synthesis of RNA and DNA (localisation between 16024 and 576 bp); CSB1, CSB2, CSB3 — conservative blocks 1, 2 and 3; 7S DNA — short third strand of mtDNA in the D-loop region; OH — origin of mtDNA heavy strand replication; OL — origin of mtDNA light strand replication; TAS — termination-associated sequence; H, L — mtDNA heavy and light strands; T, P, E, L2, S2, H, R, G, K, D, S1, A, N, C, Y, W, M, Q, I, L1, V, F — tRNA genes; CYB — cytochrome B gene; ND6, ND5, ND4, ND3, ND2, ND1 — NADH-dehydrogenase subunit genes; CO3, CO2, CO1 — cytochrome oxidase subunit genes; RNR2 and RNR1 are mitochondrial 16S and 12S ribosomal RNA genes.

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4. Fig. 3. Dynamics of changes in mitochondria during breast cancer development. The red background and red line show the increasing role of active glycolysis in cell energy production; green background and green line — reduced role of oxidative phosphorylation in cell energy production; red circles — mtDNA with a mutation; green circles are mtDNA germ lines.

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版权所有 © Tikhonov D.G., Vinokurov M.M., Kipriyanova N.S., Golubenko M.V., 2023

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