Mitophagy in human health, ageing and disease

Nature Metabolism, Год журнала: 2023, Номер 5(12), С. 2047 - 2061

Опубликована: Ноя. 30, 2023

Язык: Английский

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The multifaceted regulation of mitophagy by endogenous metabolites

Autophagy, Год журнала: 2021, Номер 18(6), С. 1216 - 1239

Опубликована: Сен. 29, 2021

Owing to the dominant functions of mitochondria in multiple cellular metabolisms and distinct types regulated cell death, maintaining a functional mitochondrial network is fundamental for homeostasis body fitness response physiological adaptations stressed conditions. The process mitophagy, which dysfunctional or superfluous are selectively engulfed by autophagosome subsequently degraded lysosome, has been well formulated as one major mechanisms quality control. To date, PINK1-PRKN-dependent receptors (including proteins lipids)-dependent pathways have characterized determine mitophagy mammalian cells. highly responsive dynamics endogenous metabolites, including iron-, calcium-, glycolysis-TCA-, NAD+-, amino acids-, fatty cAMP-associated metabolites. Herein, we summarize recent advances toward molecular details regulation We also highlight key regulations shed new light on bidirectional interplay between metabolisms, with attempting provide perspective insight into nutritional intervention metabolic disorders deficit.

Язык: Английский

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PGC-1α-Mediated Mitochondrial Quality Control: Molecular Mechanisms and Implications for Heart Failure

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Май 27, 2022

Mitochondria with structural and functional integrity are essential for maintaining mitochondrial function cardiac homeostasis. It is involved in the pathogenesis of many diseases. Peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1 ), acted as a transcriptional cofactor, abundant heart, which modulates biogenesis dynamics mitophagy to sustain steady-state mitochondria. Cumulative evidence suggests that dysregulation PGC-1 closely related onset progression heart failure. deficient-mice can lead worse under pressure overload compared sham. Here, this review mainly focuses on what known about its regulation functions, well crucial role

Язык: Английский

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Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis

Journal of Biomedical Science, Год журнала: 2023, Номер 30(1)

Опубликована: Окт. 12, 2023

Mitochondrial mass and quality are tightly regulated by two essential opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) mitophagy, in response to cellular energy needs other environmental cues. Great strides have been made uncover key regulators of these complex processes. Emerging evidence has shown that there exists a tight coordination between mitophagy mitobiogenesis, their defects may cause many human diseases. In this review, we will first summarize the recent advances discovery molecular regulations mitobiogenesis then focus on mechanism signaling pathways involved simultaneous regulation tissue or cultured cells needs, stress, pathophysiological conditions. Further studies crosstalk processes at level provide better understanding how cell maintains optimal fitness function under physiological conditions, which holds promise for fighting aging aging-related

Язык: Английский

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Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Язык: Английский

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A mitochondrial SCF‐FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease

The EMBO Journal, Год журнала: 2023, Номер 42(13)

Опубликована: Март 10, 2023

Язык: Английский

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M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1

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

Опубликована: Фев. 22, 2024

Abstract Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous discover that these have a direct beige-promoting function is independent of system. We identify adipocyte Ets1 as vital mediator this process. The anti-inflammatory M2 suppress expression adipocytes, transcriptionally activate mitochondrial biogenesis, well clearance, thereby increasing the numbers promoting beiging Male knock-in are completely cold intolerant, whereas male lacking adipocytes show enhanced energy expenditure resistant to metabolic disorders caused high-fat-diet. Our findings elucidate communication between uncover for responding negatively governing content formation.

Язык: Английский

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S100A8/A9hi neutrophils induce mitochondrial dysfunction and PANoptosis in endothelial cells via mitochondrial complex I deficiency during sepsis

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 28, 2024

Abstract S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in variety inflammatory diseases. Although S100a8/a9 has been reported trigger endothelial cell apoptosis, mechanisms S100a8/a9-induced dysfunction during sepsis require in-depth research. We demonstrate that high expression levels suppress Ndufa3 mitochondrial complex I via downregulation Nrf1 expression. Mitochondrial deficiency contributes NAD + -dependent Sirt1 suppression, which induces disorders, including excessive fission blocked mitophagy, mtDNA from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis cells. Moreover, based on comprehensive scRNA-seq bulk RNA-seq analyses, S100A8/A9 hi are closely associated with circulating count (a useful marker damage), S100A8 is an independent risk factor for poor prognosis patients.

Язык: Английский

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Mitophagy receptor FUNDC1 is regulated by PGC‐1α/NRF1 to fine tune mitochondrial homeostasis

EMBO Reports, Год журнала: 2021, Номер 22(3)

Опубликована: Фев. 8, 2021

Язык: Английский

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Mitophagy in carcinogenesis, drug resistance and anticancer therapeutics

Cancer Cell International, Год журнала: 2021, Номер 21(1)

Опубликована: Июль 5, 2021

Abstract The mitochondrion is an organelle that plays a vital role in energy production, cytoplasmic protein degradation and cell death. Mitophagy autophagic procedure specifically clears damaged mitochondria maintains its homeostasis. Emerging evidence indicates mitophagy involved many physiological processes, including cellular homeostasis, differentiation nerve protection. In this review, we describe the regulatory mechanisms of mammals yeasts highlight recent advances relevant to function carcinogenesis drug resistance. Finally, section has been dedicated describing anticancer therapeutics, which new frontier offers precise promising strategy.

Язык: Английский

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