Aug 2026· Journal of Molecular Neuroscience· Vol 76· 0 citations· 101 references
Medicine
TL;DR
This review integrates current understanding of mitochondrial permeability transition with emerging evidence implicating three novel regulatory components: F-ATP synthase inhibitory factor 1 (IF1), subunit j of F-ATP synthase, and mitochondrial carrier homolog 2 (MTCH2), expanding the therapeutic landscape for treating aging and neurodegeneration through targeting the PTP.
More research in the field may unravel the mechanistic details of the organellar crosstalk that works in concert with classical aging pathways to sustain aging progression, which may help promote healthier aging.
It is demonstrated that mitochondrial impairment precedes classical neuropathological hallmarks, thereby positioning mitochondrial dysfunction as a primary driver rather than a secondary consequence of neurodegeneration, and critically evaluates the translational landscape of mitochondria-targeted interventions.
Zhaomin Yao, Yangwa Wei, Weiming Xie et al.· Ageing Research Reviews· 0 citations
Mitochondrial reactive oxygen species (mtROS) have been implicated in aging and disease for decades and are typically viewed as a unitary, non-specific oxidative burden on cells and tissues. However, recent studies have identified at least eleven individual sources of mitochondrial ROS (ISOMRs) and revealed that ISOMRs have distinct, dynamic, and often reversible roles in diverse physiological and pathological processes, including neurodegenerative diseases, immune and metabolic dysregulation, and ischemia-reperfusion injury. This review describes the upstream molecular events that control ISOMR activity, recently developed tools for studying mtROS in general and ISOMRs more specifically, and the evolving perspectives on ISOMR roles in context-specific cell signaling. Future studies to define predictive principles of ISOMR regulation are necessary to open frontiers of redox biology and identify therapeutic strategies for selective modulation of ISOMR-dependent mechanisms in aging and disease.
Daniel Barnett, Caroline Booraem, Anna G. Orr et al.· Molecules and Cells· 0 citations
Neurodegenerative diseases have emerged as a significant global health challenge, with existing treatments merely providing symptomatic relief and failing to halt disease progression. Mitochondrial dysfunction and an imbalance in the molecular chaperone network constitute the core common pathological mechanisms underlying various neurodegenerative diseases (NDDs). These two factors collaboratively induce energy metabolism disorders, oxidative stress, calcium homeostasis imbalance, and protein homeostasis collapse, collectively driving neuronal degeneration. This article systematically elucidates the core characteristics of mitochondrial dysfunction in NDDs, dissects the molecular mechanisms by which the mitochondrial molecular chaperone network maintains mitochondrial homeostasis, summarizes therapeutic strategies for NDDs aimed at restoring mitochondrial and related molecular chaperone functions, discusses the current challenges faced in research, such as targeted delivery and clinical translation, and also proposes potential development directions for future.
Xue Xia, JiaBo Zhang, Xingyu Lin et al.· Pharmacology and Therapeutic...· 0 citations
Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na+/K+-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes.
Federica De Luca, Dario Troise, Valentina Camporeale et al.· Antioxidants· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
