Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva DOI Creative Commons
Liping Sun, Y. Jin,

Megumi Nishio

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(5), P. e202302219 - e202302219

Published: Feb. 16, 2024

Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors muscle tissues. The relevant biological processes aberrantly regulated activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed enrichment of genes involved oxidative phosphorylation (OXPHOS) during A–induced chondrogenesis mesenchymal stem derived from FOP patient–specific induced pluripotent Functional showed metabolic transition glycolysis to OXPHOS chondrogenesis, along with increased mitochondrial biogenesis. inhibition rapamycin suppressed OXPHOS, whereas inhibitor IACS-010759 inhibited cartilage matrix vitro, indicating that principally mTORC1-induced chondrogenesis. Furthermore, injury–induced fibro/adipogenic transgenic mice carrying mutated human ACVR1. These data indicated critical downstream mediator signaling therefore potential therapeutic target.

Language: Английский

The role of mitochondrial dynamics and mitophagy in skeletal muscle atrophy: from molecular mechanisms to therapeutic insights DOI Creative Commons

Yuhang Lei,

Mailin Gan,

Yanhao Qiu

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: April 23, 2024

Abstract Skeletal muscle is the largest metabolic organ of human body. Maintaining best quality control and functional integrity mitochondria essential for health skeletal muscle. However, mitochondrial dysfunction characterized by dynamic imbalance mitophagy disruption can lead to varying degrees atrophy, but underlying mechanism action still unclear. Although dynamics are two different mechanisms, a large amount evidence has indicated that they interrelated mutually regulated. The former maintains balance network, eliminates damaged or aged mitochondria, enables cells survive normally. latter degrades through lysosomal pathway, ensuring cellular homeostasis. atrophy considered an urgent global issue. Understanding gaining knowledge about caused dysfunction, particularly focusing on autophagy, greatly contribute prevention treatment atrophy. In this review, we critically summarize recent research progress in expound intrinsic molecular mitophagy. Importantly, emphasize potential targeting as therapeutic strategies including pharmacological exercise therapy, effective methods

Language: Английский

Citations

12
Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis DOI Creative Commons
Jiayin Wang, Dandan Jia, Zhiwang Zhang

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(1), P. 59 - 59

Published: Jan. 16, 2025

Background/Objectives: Sarcopenia, characterized by the progressive loss of muscle mass and strength, is linked to physical disability, metabolic dysfunction, an increased risk mortality. Exercise therapy currently acknowledged as a viable approach for addressing sarcopenia. Nevertheless, molecular mechanisms behind exercise training or activity remain poorly understood. The disruption mitochondrial homeostasis implicated in pathogenesis effectively delays onset sarcopenia significantly maintaining homeostasis, including promoting mitophagy, improving biogenesis, balancing dynamics, redox. Exerkines (e.g., adipokines, myokines, hepatokines, osteokines), signaling molecules released response training, may potentially contribute skeletal metabolism through ameliorating reducing inflammation, regulating protein synthesis defense against Methods: In this review, we provide detailed summary exercise-induced exerkines confer their benefit, with particular focus on impact context Results: induces substantial adaptations muscle, mass, improved regeneration hypertrophy, elevated hormone release, enhanced function. An expanding body research highlights that have potential regulate processes such autophagy, redox balance. These maintenance thereby supporting health. Conclusions: Through comprehensive investigation within mitochondria, reveals new insights into key exercise-protective sensors combating

Language: Английский

Citations

1
Optimised Skeletal Muscle Mass as a Key Strategy for Obesity Management DOI Creative Commons
Thomas M. Barber, Stefan Kabisch, A. Pfeiffer

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(2), P. 85 - 85

Published: Feb. 1, 2025

The ‘Body Mass Index’ (BMI) is an anachronistic and outdated ratio that used as internationally accepted diagnostic criterion for obesity, to prioritise, stratify, outcome-assess its management options. On individual level, the BMI has potential mislead, including inaccuracies in cardiovascular risk assessment. Furthermore, places excessive emphasis on a reduction overall body weight (rather than optimised composition) contributes towards misunderstanding of quiddity obesity dispassionate societal perspective response global problem. objective this review provide overview transitions away from novel vista: viewing skeletal muscle (SM). We resurrect SM tissue hidden plain sight key role plays influencing metabolic health efficiency. discuss complex interlinks between adipose (AT) through myokines adipokines, argue rather two separate tissues, AT should be considered single entity: ‘Adipo–Muscle Axis’. vicious circle sarcopenic which aging- obesity-related decline mass worsened status insulin resistance, turn further compounds function. approaches can mitigate against context negative energy balance, optimisation dietary protein intake resistance physical exercises, molecules development target SM, will play important future obesity. Finally, we Adipo–Muscle Ratio (AMR) would more clinically meaningful descriptor definition help shift our focus regarding effective merely inducing loss optimising AMR with proper attention maintenance augmentation

Language: Английский

Citations

1
Mitochondrial dynamics and quality control regulate proteostasis in neuronal ischemia-reperfusion DOI Creative Commons
Garrett M. Fogo,

Sarita Raghunayakula,

Katlynn J. Emaus

et al.

Autophagy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Mitochondrial damage and dysfunction are hallmarks of neuronal injury during cerebral ischemia-reperfusion (I/R). Critical mitochondrial functions including energy production cell signaling perturbed I/R, often exacerbating contributing to secondary injury. The integrity the proteome is essential for efficient function. proteostasis mediated by cooperative forces mitophagy intramitochondrial proteolysis. aim this study was elucidate patterns protein dynamics their key regulators an in vitro model I/R Utilizing MitoTimer reporter, we quantified oxidation turnover injury, highlighting a point at 2 h reoxygenation aged/oxidized turnover. This found be both LONP1-dependent proteolysis PRKN/parkin-dependent mitophagy. Additionally, proteostatic response mitochondria influenced fusion fission machinery. Our findings highlight involvement

Language: Английский

Citations

1
Ginsenoside Rh1 mitigates mitochondrial dysfunction induced by myocardial ischaemia through its novel role as a sirtuin 3 activator DOI Open Access
Shuaishuai Gong, Hong Chen, Shuhua Fang

et al.

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Background and Purpose The sirtuin 3 (SIRT3) signalling pathway is an essential target for various cardiovascular diseases (CVDs), although effective interventions in myocardial ischaemia‐induced mitochondrial dysfunction remain to be elucidated. Here, we discovered a potent SIRT3 activator explored its efficacy mechanism against dysfunction. Experimental Approach Molecular docking screened activators among the 10 more common rare ginsenosides. In vivo, left coronary artery ligation induced ischaemia injury, followed by echocardiography, histopathology serum biochemical indicators, C57BL/6J mice. Expression levels of mitophagy dynamics‐associated proteins were examined western blot (WB), immunofluorescence (IF) immunohistochemistry (IHC). vitro, oxygen–glucose deprivation‐induced hypoxic injury neonatal rat ventricular myocytes, cell viability function investigated. small interference RNA (siRNA) was transfected into cardiomyocytes validate dynamics regulated ginsenoside Rh1. Key Results Rh1 exhibited strongest binding affinity as SIRT3. improved cardiac mitigated vivo. ameliorated oxidative stress, network morphology respiration hypoxia‐injured cardiomyocytes. bound simultaneously up‐regulated Foxo3a, facilitating nuclear translocation reducing acetylation Foxo3a. markedly promoted fusion, inhibited fission accelerated mitophagy. siRNA abrogated regulation on Conclusion Implications novel protects dysfunction, providing new clues prevent treat ischaemic injury‐associated CVD.

Language: Английский

Citations

1
The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools DOI Open Access
Jorge Sanz‐Ros, Cristina Mas‐Bargues, Nekane Romero-García

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7005 - 7005

Published: April 10, 2023

The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant can cause severe damage to the cells, which have established tight quality control for mitochondria. This process avoids accumulation of damaged lead release mitochondrial constituents extracellular milieu through vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, protein complexes respiratory chain, largest even transport whole Macrophages ultimately engulf these undergo outsourced mitophagy. Recently, it has been reported that also contain healthy mitochondria, whose function seems be rescue stressed cells by restoring loss function. transfer opened field their use as potential disease biomarkers therapeutic tools. review describes this new EVs-mediated current application clinical environment.

Language: Английский

Citations

20
Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration DOI Creative Commons
Juan Wang, Donglin Li,

Lang-Fan Zheng

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(3), P. 384 - 399.e5

Published: Jan. 9, 2024

Language: Английский

Citations

9
Is mitochondrial morphology important for cellular physiology? DOI
Timothy Wai

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(10), P. 854 - 871

Published: June 12, 2024

Language: Английский

Citations

9
Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives DOI Creative Commons

Jiayan Huang,

Yan Zhao, Yafang Song

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(5), P. 651 - 651

Published: May 11, 2024

Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against postsynaptic membrane receptors present at neuromuscular junction. This condition characterized fatigue and muscle weakness, including diplopia, ptosis, systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, pathogenesis MG may involve mitochondrial damage ferroptosis. Mitochondria are primary site energy production, reactive oxygen species (ROS) generated due dysfunction can induce Nanomedicines have been extensively employed treat various disorders their modifiability good biocompatibility, but application management has rather limited. Nevertheless, nanodrug delivery systems carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for treatment MG. Therefore, this review focuses on nanoplatforms aimed attenuating restoring function, inhibiting potentially serve as promising agents targeted therapy.

Language: Английский

Citations

7
Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice DOI Creative Commons
F. Li, Fulong Zhang, Haiwang Shi

et al.

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(5), P. 1733 - 1749

Published: June 26, 2024

Aging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate atrophy, its specific impact on and repair MuSCs remains unclear.

Language: Английский

Citations

7