Characterization and trans-generation dynamics of mitogene pool in the silver carp (Hypophthalmichthys molitrix) DOI Creative Commons
Jinlin Li,

Hengshu Wu,

Yingna Zhou

и другие.

G3 Genes Genomes Genetics, Год журнала: 2024, Номер 14(9)

Опубликована: Июнь 26, 2024

Abstract Multicopied mitogenome are prone to mutation during replication often resulting in heteroplasmy. The derived variants a cell, organ, or an individual animal constitute mitogene pool. pool is initiated by small fraction of the egg However, characteristics and relationship between them has not yet been investigated. This study quantitatively analyzed heteroplasmy landscape, genetic loads, selection strength hatchling silver carp (Hypophthalmichthys molitrix) using high-throughput resequencing. results showed heteroplasmic sites distribute across whole both eggs hatchlings. dominant substitution was Transversion Transition hatching accounting for 95.23%±2.07% 85.38%±6.94% total HP sites, respectively. loads were 0.293±0.044 0.228±0.022 hatchlings (P=0.048). dN/dS ratio 58.03±38.98 9.44±3.93 (P=0.037). These suggest that mitogenomes under strong positive with tolerance deleterious effects, while but much weaker showing marked quality control. Based on these findings, we proposed trans-generation dynamics model explain differential development mode two oocyte maturation ontogenesis offspring. sheds light significance persistence populations subsequent integration ecological studies conservation practices.

Язык: Английский

Mitochondrial degradation: Mitophagy and beyond DOI Creative Commons
Louise Uoselis, Thanh Ngoc Nguyen, Michael Lazarou

и другие.

Molecular Cell, Год журнала: 2023, Номер 83(19), С. 3404 - 3420

Опубликована: Окт. 1, 2023

Mitochondria are central hubs of cellular metabolism that also play key roles in signaling and disease. It is therefore fundamentally important mitochondrial quality activity tightly regulated. Mitochondrial degradation pathways contribute to control networks can regulate the metabolic profile mitochondria ensure homeostasis. Here, we cover many varied ways which cells degrade or remove their unwanted mitochondria, ranging from mitophagy extrusion. The molecular signals driving these discussed, including physiological contexts under different engaged.

Язык: Английский

Процитировано

121
Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions DOI Creative Commons

Wenhan Ju,

Yuewen Zhao, Yi Yu

и другие.

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Апрель 17, 2024

Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated many age-related pathologies. Evidence supports that the of mitochondria decline mitochondrial DNA copy number negatively affect ovarian aging. However, mechanism aging still unclear. Treatment methods, including antioxidant applications, transplantation, emerging biomaterials, advanced technologies, are being used to improve function restore oocyte quality. This article reviews key evidence research updates on damage pathogenesis aging, emphasizing may accelerate lead senescence as well exploring potential methods for using mechanisms slow down

Язык: Английский

Процитировано

19
Modeling mitochondrial DNA diseases: from base editing to pluripotent stem‐cell‐derived organoids DOI Creative Commons
Isabella Tolle, Valeria Tiranti, Alessandro Prigione

и другие.

EMBO Reports, Год журнала: 2023, Номер 24(4)

Опубликована: Март 6, 2023

Abstract Mitochondrial DNA (mtDNA) diseases are multi‐systemic disorders caused by mutations affecting a fraction or the entirety of mtDNA copies. Currently, there no approved therapies for majority diseases. Challenges associated with engineering have in fact hindered study defects. Despite these difficulties, it has been possible to develop valuable cellular and animal models Here, we describe recent advances base editing generation three‐dimensional organoids from patient‐derived human‐induced pluripotent stem cells (iPSCs). Together already available modeling tools, combination novel technologies could allow determining impact specific distinct human cell types might help uncover how mutation load segregates during tissue organization. iPSC‐derived also represent platform identification treatment strategies probing vitro effectiveness gene therapies. These studies potential increase our mechanistic understanding may open way highly needed personalized therapeutic interventions.

Язык: Английский

Процитировано

20
FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis DOI Creative Commons
Guibin Fang, Xingzhao Wen, Zongrui Jiang

и другие.

Molecular Therapy, Год журнала: 2023, Номер 31(12), С. 3594 - 3612

Опубликована: Окт. 14, 2023

Язык: Английский

Процитировано

17
Maternal age enhances purifying selection on pathogenic mutations in complex I genes of mammalian mtDNA DOI

Yanfei Ru,

Xiaoling Deng,

Jiatong Chen

и другие.

Nature Aging, Год журнала: 2024, Номер 4(9), С. 1211 - 1230

Опубликована: Июль 29, 2024

Язык: Английский

Процитировано

5
Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control DOI Creative Commons

Annabel Qi En Ng,

Seow Neng Chan, Jun Wei Pek

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 10, 2024

Abstract Mitochondria are inherited exclusively from the mothers and required for proper development of embryos. Hence, germline mitochondrial quality is highly regulated during oogenesis to ensure oocyte viability. How nutrient availability influences control unclear. Here we find that fasting leads accumulation clumps arrest in Drosophila . Fasting induces downregulation DIP1-Clueless pathway, leading an increase expression a stable intronic sequence RNA called sisR-1 Mechanistically, localizes inhibit poly-ubiquitination outer protein Porin/VDAC1, thereby suppressing p62-mediated mitophagy. Alleviation fasting-induced high levels by either RNAi or refeeding mitophagy, resumption improvement quality. Thus, our study provides possible mechanism which can improve modulating pathway. Of note, uncover response also regulates clumping deprivation, heat shock aging, suggesting broader role this control.

Язык: Английский

Процитировано

4
Mitophagy at the oocyte-to-zygote transition promotes species immortality DOI Open Access
Siddharthan Balachandar Thendral,

Sasha Bacot,

Katherine Morton

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract The quality of inherited mitochondria determines embryonic viability 1 , metabolic health during adulthood and future generation endurance. oocyte is the source all zygotic 2 mitochondrial under strict developmental regulation early oogenesis 3–5 . Yet, fully developed oocytes exhibit presence deleterious DNA (mtDNA) 6,7 dysfunction from high levels endogenous reactive oxygen species 8 exogenous toxicants 9 How prevent transmission damaged to zygotes unknown. Here we discover that onset oocyte-to-zygote transition (OZT) developmentally triggers a robust rapid mitophagy event term at OZT (MOZT). We show MOZT requires fragmentation, activation macroautophagy system receptor FUNDC1, but not prevalent factors PINK1 BNIP3. Oocytes upregulate expression FUNDC1 in response diverse insults, including mtDNA mutations damage, uncoupling stress, dysfunction, thereby promoting selection against mitochondria. Loss leads increased inheritance impaired bioenergetic progeny, resulting diminished extinction descendent populations. Our findings reveal FUNDC1-mediated as mechanism preserves mother-to-offspring promotes continuity. These results may explain how mature many harboring mutant give rise healthy embryos with reduced mtDNA.

Язык: Английский

Процитировано

0
Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes DOI

Ritoprova Sen,

Cuckoo Teresa Jetto,

Ravi Manjithaya

и другие.

Journal of Biosciences, Год журнала: 2024, Номер 49(1)

Опубликована: Фев. 19, 2024

Язык: Английский

Процитировано

3
Mitochondrial DNA competition: starving out the mutant genome DOI Creative Commons
Antonella Spinazzola, Diego Pérez‐Rodríguez, Jan Ježek

и другие.

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(3), С. 225 - 242

Опубликована: Фев. 23, 2024

High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation such mutants may also contribute common disorders. Thus, selecting against these is a major goal in medicine. Although mutant mtDNA can drift randomly, mounting evidence indicates that active forces play role selection for variants. The underlying mechanisms are beginning be clarified, recent studies suggest metabolic cues, including fuel availability, shaping heteroplasmy. In context pathological mtDNAs, remodeling nutrient metabolism supports mitochondria with deleterious mtDNAs enables them outcompete functional owing replicative advantage. elevated requirement represents Achilles' heel because small molecules restrict consumption or interfere sensing purge cells restore respiration. These advances herald dawn new era small-molecule therapies counteract mtDNAs.

Язык: Английский

Процитировано

3
Evolution and maintenance of mtDNA gene content across eukaryotes DOI Creative Commons
Shibani Veeraragavan, Maria Vang Johansen, Iain G. Johnston

и другие.

Biochemical Journal, Год журнала: 2024, Номер 481(15), С. 1015 - 1042

Опубликована: Авг. 5, 2024

Across eukaryotes, most genes required for mitochondrial function have been transferred to, or otherwise acquired by, the nucleus. Encoding in nucleus has many advantages. So why do mitochondria retain any at all? Why does set of mtDNA vary so much across different species? And how species maintain functionality they retain? In this review, we will discuss some possible answers to these questions, attempting a broad perspective eukaryotes. We hope cover interesting features which may be less familiar from particular species, including ubiquity recombination outside bilaterian animals, encrypted chainmail-like mtDNA, single split over multiple chromosomes, triparental inheritance, gene transfer by grafting, gain factors, social networks mitochondria, and role dysfunction feeding world. unifying picture where organismal ecology gene-specific together influence whether organism X retains Y, development determine strategies, importantly recombination, are used that retained.

Язык: Английский

Процитировано

3