Moving beyond the Tip of the Iceberg: DJ-1 Implications in Cancer Metabolism DOI Creative Commons
Erika Olivo,

Marina La Chimia,

Jessica Ceramella

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(9), P. 1432 - 1432

Published: April 23, 2022

DJ-1, also called Parkinson’s protein 7 (PARK7), is ubiquitously expressed and plays multiple actions in different physiological and, especially, pathophysiological processes, as evidenced by its identification neurodegenerative diseases high expression types of cancer. To date, the exact activity DJ-1 carcinogenesis has not been fully elucidated, however several recent studies disclosed involvement regulating fundamental pathways involved cancer onset, development, metastatization. At this purpose, we have dissected role maintaining transformed phenotype, survival, drug resistance, metastasis formation, differentiation cells. Moreover, discussed controlling redox status cells, along with ability to attenuate reactive oxygen species (ROS)-dependent cell death, well mediate ferropotosis. Finally, a mention development therapeutic strategies targeting done. We reported most studies, aiming shed light on played aspects create foundation for moving beyond tip iceberg.

Language: Английский

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging DOI Open Access
Jean‐Philippe Leduc‐Gaudet, Sabah N. A. Hussain, Esther Barreiro

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8179 - 8179

Published: July 30, 2021

The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range cellular processes, including energy supply, Ca2+ homeostasis, retrograde signaling, cell death, and many others. All mitochondria-containing cells, skeletal dispose several pathways to maintain health, biogenesis, mitochondrial-derived vesicles, dynamics (fusion fission process shaping morphology), mitophagy-the charge the removal mitochondria though autophagy. loss mass (atrophy) major health problem worldwide, especially older people. Currently, there no treatment counteract progressive decline strength that occurs with aging, termed sarcopenia. There increasing data, our own, suggesting accumulation dysfunctional contributes development Impairments mitophagy were recently proposed contribute This review summarizes current state knowledge on role played by We also highlight recent studies showing enhancing promising therapeutic target prevent or even treat dysfunction elderly.

Language: Английский

Citations

175
Mitochondrial dysfunction: roles in skeletal muscle atrophy DOI Creative Commons
Xin Chen, Yanan Ji, Ruiqi Liu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 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.

Language: Английский

Citations

114
Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies DOI
Gökhan Burçin Kubat, Esmaa Bouhamida, Öner Ülger

et al.

Mitochondrion, Journal Year: 2023, Volume and Issue: 72, P. 33 - 58

Published: July 13, 2023

Language: Английский

Citations

53
Circulating exosome‐like vesicle and skeletal muscle microRNAs are altered with age and resistance training DOI Creative Commons

Donald Xhuti,

Mats I. Nilsson,

Katherine Manta

et al.

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(22), P. 5051 - 5073

Published: Feb. 1, 2023

The age-related loss of skeletal muscle mass and functionality, known as sarcopenia, is a critical risk factor for morbidity all-cause mortality. Resistance exercise training (RET) the primary countermeasure to fight sarcopenia ageing. Altered intercellular communication hallmark ageing, which not well elucidated. Circulating extracellular vesicles (EVs), including exosomes, contribute by delivering microRNAs (miRNAs), modulate post-translational modifications, have been shown be released following exercise. There little evidence regarding how EVs or EV-miRNAs are altered with age RET. Therefore, we sought characterize circulating in young older individuals, prior 12-week resistance programme. Plasma were isolated using size exclusion chromatography ultracentrifugation. We found that ageing reduced expression markers CD9, CD81. Using late-passage human myotubes model vitro, show significantly lower secreted exosome-like (ELVs). Further, levels ELV-miRNAs associated health individuals at baseline but increased RET comparable young. Muscle biopsies similar reductions miRNA expressions, largely no effect training. This reflected where aged endogenous muscle-specific miRNAs (myomiRs). Lastly, proteins ELV biogenesis higher both tissues myotubes. Together affects cargo biogenesis, release. can partially normalize this communication. KEY POINTS: reduces vesicle (ELV) markers, CD9 vitro. find increase (RET). In muscle, Late-passage also appear aberrant production myomiRs abundance than youthful counterparts myotubes, involved ELV- upregulated.

Language: Английский

Citations

29
The Role of Mitophagy in Skeletal Muscle Damage and Regeneration DOI Creative Commons

Eirini Chatzinikita,

Μaria Maridaki, Konstantinos Palikaras

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 716 - 716

Published: Feb. 24, 2023

Mitochondria are cellular organelles that play an essential role in generating the chemical energy needed for biochemical reactions cells. Mitochondrial biogenesis, i.e., de novo mitochondria formation, results enhanced respiration, metabolic processes, and ATP generation, while autophagic clearance of (mitophagy) is required to remove damaged or useless mitochondria. The balance between opposing processes mitochondrial biogenesis mitophagy highly regulated crucial maintenance number function as well homeostasis adaptations demands extracellular stimuli. In skeletal muscle, maintaining homeostasis, network exhibits complex behaviors undergoes dynamic remodeling response various conditions pathologies characterized by changes muscle cell structure metabolism, such exercise, damage, myopathies. particular, involvement mediating regeneration following damage has received increased attention, modifications mitophagy-related signals arise from variations restructuring pathways can lead partial impaired function. Muscle (through myogenesis) exercise-induced a regulated, rapid turnover poor-functioning mitochondria, permitting synthesis better-functioning occur. Nevertheless, aspects during remain poorly understood warrant further characterization. this review, we focus on critical proper highlighting molecular mechanisms mitophagy-associated dynamics reformation.

Language: Английский

Citations

28
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
Redox regulation of UPR signalling and mitochondrial ER contact sites DOI Creative Commons

Jose C. Casas-Martinez,

Afshin Samali, Brian McDonagh

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: June 7, 2024

Mitochondria and the endoplasmic reticulum (ER) have a synergistic relationship are key regulatory hubs in maintaining cell homeostasis. Communication between these organelles is mediated by mitochondria ER contact sites (MERCS), allowing exchange of material information, modulating calcium homeostasis, redox signalling, lipid transfer regulation mitochondrial dynamics. MERCS dynamic structures that allow cells to respond changes intracellular environment under normal homeostatic conditions, while their assembly/disassembly affected pathophysiological conditions such as ageing disease. Disruption protein folding lumen can activate Unfolded Protein Response (UPR), promoting remodelling membranes formation. The UPR stress receptor kinases PERK IRE1, located at or close MERCS. signalling be adaptive maladaptive, depending on whether disruption transient sustained. Adaptive via increase import, metabolism dynamics, maladaptive result excessive import activation apoptotic pathways. Targeting assembly an attractive therapeutic approach for range age-related neurodegeneration sarcopenia. This review highlights emerging evidence related role orchestrating inter-organelle communication mitochondria, ultimately determination function fate.

Language: Английский

Citations

11
MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging DOI Creative Commons
Yunfei Yang, Yang Wu,

Zhiyin Liao

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(12)

Published: Nov. 29, 2021

Abstract Age-related loss of skeletal muscle mass and function, termed sarcopenia, could impair the quality life in elderly. The mechanisms involved aging are intricate largely unknown. However, more evidence demonstrated that mitochondrial dysfunction apoptosis also play an important role aging. Recent studies have shown calcium uniporter (MCU)-mediated affects function by affecting function. During aging, we observed downregulated expression uptake family member3 (MICU3) muscle, a regulator MCU, which resulted significant reduction uptake. MICU3 remains poorly understood. Therefore, investigated effect on aged mice senescent C2C12 cells induced d -gal. Downregulation was associated with decreased myogenesis but increased oxidative stress apoptosis. Reconstitution enhanced antioxidants, prevented accumulation ROS, apoptosis, myogenesis. These findings indicate might promote Ca 2+ homeostasis attenuate restore may be potential therapeutic target

Language: Английский

Citations

49
The importance of mitochondrial quality control for maintaining skeletal muscle function across health span DOI

James Sligar,

Danielle Debruin, Nicholas J. Saner

et al.

AJP Cell Physiology, Journal Year: 2022, Volume and Issue: 322(3), P. C461 - C467

Published: Feb. 2, 2022

As the principal energy-producing organelles of cell, mitochondria support numerous biological processes related to metabolism, growth, and regeneration in skeletal muscle. Deterioration muscle functional capacity with age is thought be driven part by a reduction oxidative reduced fatigue resistance. Underlying this maladaptive response development mitochondrial dysfunction caused alterations quality control (MQC), term encompassing synthesis (biogenesis), remodeling (dynamics), degradation (mitophagy). Knowledge regarding role regulation MQC influence aging process has rapidly advanced past decade. Given emerging link between MQC, therapeutic approaches manipulate prevent during hold tremendous potential.

Language: Английский

Citations

35
Peroxiredoxin 2 is required for the redox mediated adaptation to exercise DOI Creative Commons
Xia Qin,

José C. Casas-Martinez,

Eduardo Zarzuela

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 60, P. 102631 - 102631

Published: Feb. 9, 2023

Exercise generates a site-specific increase in Reactive Oxygen Species (ROS) within muscle that promotes changes gene transcription and mitochondrial biogenesis, required for the beneficial adaptive response. We demonstrate Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxiredoxin, is hormesis response to physiological levels of H2O2 myoblasts following exercise C. elegans. A short bolus addition increases capacity improves myogenesis cultured myoblasts, this was suppressed with decreased expression Prdxs. Moreover, swimming protocol elegans increased content, fitness, survival longevity wild type (N2) worms. In contrast, prdx-2 mutant worms had disrupted mitochondria, reduced lifespan exercise. Global proteomics identified distinct proteome N2 mutants. Furthermore, redox proteomic approach quantify reversible oxidation specific Cysteine residues revealed more state non-exercised strain become oxidized Cys from regulatory proteins exercise, establishing key role PRDX-2 signalling cascade endogenous ROS generation. Our results conserved Peroxiredoxins are stress.

Language: Английский

Citations

18