Role of inner mitochondrial protein OPA1 in mitochondrial dysfunction by tobacco smoking and in the pathogenesis of COPD DOI Creative Commons
Krishna P. Maremanda, Isaac K. Sundar, Irfan Rahman

и другие.

Redox Biology, Год журнала: 2021, Номер 45, С. 102055 - 102055

Опубликована: Июнь 24, 2021

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic fibrosis (IPF) are linked to several mitochondrial alterations. Cigarette smoke (CS) alters the structure function of mitochondria. OPA1 is main inner GTPase responsible for fusion events. undergoes proteolytic cleavage from long short forms during acute stress mitophagy. However, exact role isoforms related proteins CS-induced mitophagy COPD not clear. Lung tissues non-smokers, smokers, IPF were used determine relative expression proteins. Additionally, we mouse lungs (6 months) CS exposure evaluate status OPA1. Primary fibroblasts normal patients naked mole rat (NMR) fibroblasts, human fetal fibroblast (HFL1), embryonic wild type (WT), OPA1−/−, MFN1 MFN2−/− effect on isoforms. Various promoters/activators (BGP-15, leflunomide, M1) fission inhibitor (DRP1) their cigarette extract (CSE)-induced epithelial (BEAS2B) cell damage, respectively. Seahorse flux analyzer was these compounds in BEAS2B cells with without CSE exposure. Short predominantly detected significantly increased subjects. Acute treatment various lines except NMR found increase conversion stress-related protein SLP2 all used. interacting partners like prohibitins (PHB1 2) also altered depending Finally, BGP-15 leflunomide able preserve isoform treated CSE. The along play a crucial causing mitophagy/mitochondrial dysfunction COPD, which may be novel therapeutic target COPD.

Язык: Английский

Mitochondrial dynamics in health and disease: mechanisms and potential targets DOI Creative Commons
Wen Chen,

Huakan Zhao,

Yongsheng Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 6, 2023

Abstract Mitochondria are organelles that able to adjust and respond different stressors metabolic needs within a cell, showcasing their plasticity dynamic nature. These abilities allow them effectively coordinate various cellular functions. Mitochondrial dynamics refers the changing process of fission, fusion, mitophagy transport, which is crucial for optimal function in signal transduction metabolism. An imbalance mitochondrial can disrupt function, leading abnormal fate, range diseases, including neurodegenerative disorders, cardiovascular diseases cancers. Herein, we review mechanism dynamics, its impacts on function. We also delve into changes occur during health disease, offer novel perspectives how target modulation dynamics.

Язык: Английский

Процитировано

375
Reciprocal Regulation of Mitochondrial Fission and Fusion DOI
Rasha Sabouny, Timothy E. Shutt

Trends in Biochemical Sciences, Год журнала: 2020, Номер 45(7), С. 564 - 577

Опубликована: Апрель 11, 2020

Язык: Английский

Процитировано

166
Mitochondria and Critical Illness DOI

Gerald S. Supinski,

Elizabeth A. Schroder, Leigh Ann Callahan

и другие.

CHEST Journal, Год журнала: 2019, Номер 157(2), С. 310 - 322

Опубликована: Сен. 5, 2019

Язык: Английский

Процитировано

156
Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities DOI Creative Commons
Jannik Prasuhn, Ryan L. Davis, Kishore R. Kumar

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 8

Опубликована: Янв. 5, 2021

The underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This supported by already large rapidly growing body evidence showing that the role (dys)function central multifaceted. However, there are clear gaps in knowledge, including dilemma explaining why inherited mitochondriopathies do not usually present with parkinsonian symptoms. Many aspects function potential therapeutic targets, reactive oxygen species production, mitophagy, biogenesis, dynamics trafficking, metal ion homeostasis, sirtuins, endoplasmic reticulum links mitochondria. Potential strategies may also incorporate exercise, microRNAs, transplantation, stem cell therapies, photobiomodulation. Despite multiple studies adopting numerous treatment strategies, clinical trials to date have generally failed show benefit. To overcome this hurdle, more accurate biomarkers required detect subtle beneficial effects. Furthermore, selecting study participants early course, studying them for suitable durations, stratifying according genetic neuroimaging findings increase likelihood successful trials. Moreover, treatments involving combined approaches will likely better address complexity disease. Therefore, right patients, at time, using targeted combination treatments, offer best chance development effective novel therapy targeting

Язык: Английский

Процитировано

108
Mitochondrial dysfunction: roles in skeletal muscle atrophy DOI Creative Commons
Xin Chen, Yanan Ji, Ruiqi Liu

и другие.

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июль 26, 2023

Abstract Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, damage to mitochondria can lead a series of pathophysiological changes. Mitochondrial dysfunction atrophy, its molecular mechanism leading atrophy is complex. Understanding the pathogenesis mitochondrial useful for prevention treatment finding drugs methods target modulate function are urgent tasks atrophy. In this review, we first discussed normal muscle. Importantly, described effect on mechanisms involved. Furthermore, regulatory different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 NF-κB pathways, etc.) factors were investigated dysfunction. Next, analyzed manifestations caused by diseases. Finally, summarized preventive therapeutic effects targeted regulation including drug therapy, exercise diet, gene stem cell therapy physical therapy. This review great significance holistic understanding role muscle, which helpful researchers further has an inspiring development strategies targeting future.

Язык: Английский

Процитировано

107
Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance DOI

Sun Danan,

Jin Wang, Sam Toan

и другие.

Angiogenesis, Год журнала: 2022, Номер 25(3), С. 307 - 329

Опубликована: Март 18, 2022

Язык: Английский

Процитировано

88
Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy DOI Creative Commons
Ying Jiang, Sarah Krantz,

Xiang Qin

и другие.

Redox Biology, Год журнала: 2022, Номер 52, С. 102304 - 102304

Опубликована: Апрель 6, 2022

As essential regulators of mitochondrial quality control, dynamics and mitophagy play key roles in maintenance metabolic health cellular homeostasis. Here we show that knockdown the membrane-inserted scaffolding structural protein caveolin-1 (Cav-1) expression tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered morphology, increased matrix mixing, fusion fission well MDA-MB-231 triple negative breast cancer cells. Further, found interaction with fusion/fission machinery Mitofusin 2 (Mfn2) Dynamin related 1 (Drp1) was enhanced by Y14D indicating Y14 phosphorylation prevented Mfn2 Drp1 translocation mitochondria. Moreover, limiting recruitment diminished formation PINK1/Mfn2/Parkin complex required for initiation resulting accumulation damaged mitochondria ROS (mtROS). Thus, these studies indicate phospho-Cav-1 may be an important switch mechanism cell survival which could lead novel strategies complementing therapies.

Язык: Английский

Процитировано

88
Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics DOI Creative Commons
Juliane C. Campos, Luiz H. M. Bozi, Bárbara Nunes Krum

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(2)

Опубликована: Янв. 3, 2023

Exercise is a nonpharmacological intervention that improves health during aging and valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality metabolism. Mitochondrial fission fusion are critical effectors plasticity, which allows fine-tuned regulation organelle connectiveness, size, function. Here we have investigated role dynamics model organism Caenorhabditis elegans. We show body-wall single session induces cycle fragmentation followed by after recovery period, daily sessions delay physical fitness decline occur with aging. Maintenance proper essential for fitness, its enhancement training, exercise-induced remodeling proteome. Surprisingly, among long-lived genotypes analyzed (isp-1,nuo-6, daf-2, eat-2, CA-AAK-2), constitutive activation AMP-activated protein kinase (AMPK) uniquely preserves aging, benefit abolished impairment or fusion. AMPK also required to be enhanced exercise, our findings together suggesting may enhance muscle function through dynamics. Our results indicate connectivity maintaining responsiveness suggest recapitulate some benefits. Targeting mechanisms optimize fusion, as well activation, represent promising strategies promoting

Язык: Английский

Процитировано

57
Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives DOI Open Access
Marco D’Amato, Francesca Morra, Ivano Di Meo

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1969 - 1969

Опубликована: Янв. 19, 2023

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial (mtDNA). Current therapies still far from being fully effective and covering the broad spectrum of mtDNA. For example, unlike heteroplasmic conditions, MDs caused homoplasmic mtDNA do not yet benefit advances molecular approaches. An attractive method providing dysfunctional cells and/or tissues with healthy mitochondria is transplantation. In this review, we discuss what known about intercellular transfer methods used to both vitro vivo, provide an outlook on future therapeutic applications. Overall, containing wild-type copies could induce a shift even when variants present, aim attenuating preventing progression pathological clinical phenotypes. summary, transplantation challenging but potentially ground-breaking option for treatment various pathologies, although several questions remain be addressed before its application medicine.

Язык: Английский

Процитировано

41
Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases? DOI Open Access
Alexis Díaz‐Vegas, Pablo Sánchez-Aguilera, James R. Krycer

и другие.

Endocrine Reviews, Год журнала: 2020, Номер 41(3)

Опубликована: Март 16, 2020

Abstract Mitochondrial damage is implicated as a major contributing factor for number of noncommunicable chronic diseases such cardiovascular diseases, cancer, obesity, and insulin resistance/type 2 diabetes. Here, we discuss the role mitochondria in maintaining cellular whole-organism homeostasis, mechanisms that promote mitochondrial dysfunction, this phenomenon diseases. We also review state art regarding preclinical evidence associated with regulation function development current mitochondria-targeted therapeutics to treat Finally, give an integrated vision how these metabolic

Язык: Английский

Процитировано

127