ISGylation of DRP1 closely balances other post-translational modifications to mediate mitochondrial fission DOI Creative Commons

Palamou Das,

Oishee Chakrabarti

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 2, 2024

Abstract Dynamin related protein 1 (DRP1), a pivotal mitochondrial fission protein, is post-translationally modified by multiple mechanisms. Here we identify new post-translational modification of DRP1 the ubiquitin-like interferon-stimulated gene 15 (ISG15). ISGylation mediated ISG15 E3 ligase, HERC5; this promotes fission. DeISGylation however leads to hyperfusion. Heterologous expression SARS-CoV2 PLpro, deISGylating enzyme, results in similar filamentation, significant decrease total levels and efflux mtDNA. We report that deISGylated gets ubiquitylated degraded TRIM25, instead PARKIN MITOL. While cytosolic pool primarily ISGylated, both fractions may be ubiquitylated. It known phosphorylation at S616 residue regulates its localisation; show phospho-DRP1 (S616) renders competence mitochondria. This because affects functionality dynamics Alzheimer’s disease pathophysiology.

Language: Английский

Mitochondria in health, disease, and aging DOI
John S. Harrington, Stefan W. Ryter, Maria Plataki

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2349 - 2422

Published: April 6, 2023

Mitochondria are well known as organelles responsible for the maintenance of cellular bioenergetics through production ATP. Although oxidative phosphorylation may be their most important function, mitochondria also integral synthesis metabolic precursors, calcium regulation, reactive oxygen species, immune signaling, and apoptosis. Considering breadth responsibilities, fundamental metabolism homeostasis. Appreciating this significance, translational medicine has begun to investigate how mitochondrial dysfunction can represent a harbinger disease. In review, we provide detailed overview metabolism, bioenergetics, dynamics, autophagy, damage-associated molecular patterns, mitochondria-mediated cell death pathways, at any these levels is associated with disease pathogenesis. Mitochondria-dependent pathways thereby an attractive therapeutic target ameliorating human

Language: Английский

Citations

281
The role of mitochondrial fission in cardiovascular health and disease DOI
Justin M. Quiles, Åsa B. Gustafsson

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(11), P. 723 - 736

Published: May 6, 2022

Language: Английский

Citations

157
Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature DOI Creative Commons
Aalekhya Reddam, Sarah M. McLarnan, Allison Kupsco

et al.

Current Environmental Health Reports, Journal Year: 2022, Volume and Issue: 9(4), P. 631 - 649

Published: July 28, 2022

Abstract Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences extend beyond the cell. already susceptible to damage, which be exacerbated by environmental exposures. Therefore, aim this review is summarize recent literature (2012–2022) looking at effects six ubiquitous classes compounds on in human populations. Recent Findings The suggests there a number biomarkers commonly used identify dysfunction, each with certain advantages limitations. Classes toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, nanomaterials can damage mitochondria varied ways, changes mtDNA copy measures oxidative most measured Other include membrane potential, calcium levels, ATP levels. Summary This identifies characterize but emerging biomarkers, cell-free blood cardiolipin provide greater insight into impacts exposures function. using novel approaches addition well-characterized ones create standardized protocols. We identified dearth studies populations exposed chemicals, nanoparticles gap knowledge needs attention.

Language: Английский

Citations

74
Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control DOI

Xingyu Long,

Min Liu,

Yayun Nan

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

Citations

29
Targeting mitophagy in neurodegenerative diseases DOI
Odetta Antico, Paul Thompson, Nicholas T. Hertz

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

8
Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions DOI Creative Commons
И. Ф. Беленичев, Olena Popazova, Nina Bukhtiyarova

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 108 - 108

Published: Jan. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Language: Английский

Citations

2
Targeting Mitochondria in Diabetes DOI Open Access
Nina Krako Jakovljevic, Kasja Pavlović, Aleksandra Jotić

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6642 - 6642

Published: June 21, 2021

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies inability tissues to respond and leads disturbed metabolic homeostasis. Mitochondria, as a central player in cellular energy metabolism, are involved mechanisms IR T2D. Mitochondrial function affected different tissues, among skeletal muscle liver have highest impact on whole-body glucose This review focuses human studies that assess mitochondrial liver, blood cells context Furthermore, interventions targeting mitochondria T2D listed, with selection using respirometry measure function, for better data comparison. Altogether, respiratory capacity appears be indicator since it decreases disease progresses but increases after lifestyle (exercise) pharmacological interventions, together improvement health. Finally, novel therapeutics developed target potential more integrative therapeutic approach, treating both causative secondary defects diabetes.

Language: Английский

Citations

68
Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration DOI Creative Commons
Giacoma Galizzi, Marta Di Carlo

Biology, Journal Year: 2022, Volume and Issue: 11(6), P. 943 - 943

Published: June 20, 2022

Insulin was discovered and isolated from the beta cells of pancreatic islets dogs is associated with regulation peripheral glucose homeostasis. produced in brain related to synaptic plasticity memory. Defective insulin signaling plays a role dysfunction, such as neurodegenerative disease. Growing evidence suggests link between metabolic disorders, diabetes obesity, diseases, especially Alzheimer’s disease (AD). This association due common state resistance (IR) mitochondrial dysfunction. review takes journey into past summarize what known about physiological pathological tissues brain. Then, it will land present analyze on health effects diseases that are IR-dependent. Specifically, we focus our attention quality control mitochondria (MQC), dynamics, biogenesis, selective autophagy (mitophagy), healthy altered cases. Finally, this be projected toward future by examining most promising treatments target cure disorders.

Language: Английский

Citations

41
Targeting an allosteric site in dynamin-related protein 1 to inhibit Fis1-mediated mitochondrial dysfunction DOI Creative Commons
Luis Ríos, Suman Pokhrel, Sin‐Jin Li

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 19, 2023

The large cytosolic GTPase, dynamin-related protein 1 (Drp1), mediates both physiological and pathological mitochondrial fission. Cell stress triggers Drp1 binding to Fis1 subsequently, fragmentation, ROS production, metabolic collapse, cell death. Because also fission by Mff, therapeutics that inhibit should spare P110, a peptide inhibitor of Drp1-Fis1 interaction, reduces pathology in numerous models neurodegeneration, ischemia, sepsis without blocking the functions Drp1. Since peptides have pharmacokinetic limitations, we set out identify small molecules mimic P110's benefit. We map P110-binding site switch I-adjacent grove (SWAG) on Screening for SWAG-binding identifies SC9, which mimics benefits cells mouse model endotoxemia. suggest discovered this study may reduce burden Drp1-mediated pathologies potentially associated with other members GTPase family.

Language: Английский

Citations

35
Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy DOI
Jangampalli Adi Pradeepkiran,

Javaria Baig,

Ann Seman

et al.

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(4), P. 440 - 457

Published: Jan. 3, 2023

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in brain, which leads to loss neurons. Under microscope, function mitochondria uniquely primed play a pivotal role neuronal cell survival, energy metabolism, death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, defective mitophagy neurons are early indicators AD. This review article summarizes latest development AD: 1) mechanism pathways, 2) importance functions, 3) metabolic pathways 4) link between dysfunction mechanisms AD, 5) potential mitochondrial-targeted therapeutics interventions treat patients with

Language: Английский

Citations

29