Mitochondrial heterogeneity in diseases

Abstract

As key organelles involved in cellular metabolism, mitochondria frequently undergo adaptive changes in morphology, components and functions in response to various environmental stresses and cellular demands. Previous studies of mitochondria research have gradually evolved, from focusing on morphological change analysis to systematic multiomics, thereby revealing the mitochondrial variation between cells or within the mitochondrial population within a single cell. The phenomenon of mitochondrial variation features is defined as mitochondrial heterogeneity. Moreover, mitochondrial heterogeneity has been reported to influence a variety of physiological processes, including tissue homeostasis, tissue repair, immunoregulation, and tumor progression. Here, we comprehensively review the mitochondrial heterogeneity in different tissues under pathological states, involving variant features of mitochondrial DNA, RNA, protein and lipid components. Then, the mechanisms that contribute to mitochondrial heterogeneity are also summarized, such as the mutation of the mitochondrial genome and the import of mitochondrial proteins that result in the heterogeneity of mitochondrial DNA and protein components. Additionally, multiple perspectives are investigated to better comprehend the mysteries of mitochondrial heterogeneity between cells. Finally, we summarize the prospective mitochondrial heterogeneity-targeting therapies in terms of alleviating mitochondrial oxidative damage, reducing mitochondrial carbon stress and enhancing mitochondrial biogenesis to relieve various pathological conditions. The possibility of recent technological advances in targeted mitochondrial gene editing is also discussed.

Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson’s Disease Patients

“…However, as we have shown, these cells can be a promising and convenient model for studying the relationship between MN morphology and pathology associated with neurodegeneration. Furthermore, recent articles have shown that the MN can be a target for regulation of stem cell differentiation and for relieving various pathological conditions [50,51]. This is of great interest in light of the fact that neurons can be obtained from the fibroblasts of patients with PD to replace dead cells in the brain.…”

Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption

“…Recent study has also demonstrated that cell lineage-specific mitochondrial gene expression emerges early in development which contributes to the tissue specificity 20 . And our group also reviewed the mitochondria heterogeneity between different cells 58 . And mitochondria have been increasingly recognized as the important information process system beyond the traditional role of powerhouse 29 , 59 .…”

Non-coding RNA and reprogrammed mitochondrial metabolism in genitourinary cancer

“…The cancer cells rely only on glycolysis to meet their bioenergetic demands, but they still are dependent on some of the mitochondrial electron transport (mETC) byproducts for effective cell proliferation. This suggests that respiratory defects or dysfunction in mitochondrial dynamics could be the primary cause of cancer, as observed by Otto Warburg in the ‘Warburg effect ( Cantor and Sabatini, 2012 ; Ward and Thompson, 2012 ; Chen et al, 2023 ; Kaur et al, 2023 ; Wang and Patti, 2023 ). These discoveries emphasize the impact of mitochondrial function in cancer progression and could have significant implications for cancer treatment.…”

“…These discoveries emphasize the impact of mitochondrial function in cancer progression and could have significant implications for cancer treatment. Additionally, mitochondria are linked to redox regulation, cell signaling, apoptosis, and cell function and fate ( DeBerardinis and Chandel, 2016 ; Chen et al, 2023 ). Furthermore, various studies revealed that mitochondrial metabolic reprogramming is related to the development of genitourinary cancer such as bladder cancer, prostate cancer, and kidney cancer.…”