Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance DOI Creative Commons
Karolina Borankova,

Matyas Solny,

Mária Krchniaková

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 8(2), P. e202402870 - e202402870

Published: Dec. 6, 2024

Specific patterns of mitochondrial dynamics have been repeatedly reported to promote drug resistance in cancer. However, whether targeting fission– and fusion–related proteins could be leveraged combat multidrug-resistant pediatric sarcomas is poorly understood. Here, we demonstrated that the expression activation fission mediator DRP1 are affected by chemotherapy exposure common sarcomas, namely, rhabdomyosarcoma osteosarcoma. Unexpectedly, decreasing activity through stable knockdown neither attenuated sarcoma nor growth rate or network morphology. The minimal impact on cell physiology, along with up-regulation adaptor (MFF FIS1) detected cells, suggests an alternative DRP1-independent mechanism may efficiently compensate for lack activity. By exploring upstream mitophagy regulator, AMPKα1, found markedly reduced AMPKα1 levels sufficient maintain AMPK signaling capacity without affecting chemosensitivity. Collectively, our findings challenge direct involvement highlight complexity yet-to-be-characterized noncanonical regulators dynamics.

Language: Английский

Mitochondrial protein import stress DOI
Nikolaus Pfanner, Fabian den Brave, Thomas Becker

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

Citations

3
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
Opa1 processing is dispensable in mouse development but is protective in mitochondrial cardiomyopathy DOI Creative Commons
Sofia Ahola, Lilli A. Pazurek,

Fiona Carola Mayer

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(31)

Published: Aug. 2, 2024

Mitochondrial fusion and fission accompany adaptive responses to stress altered metabolic demands. Inner membrane cristae morphogenesis depends on optic atrophy 1 (Opa1), which is expressed in different isoforms cleaved from a membrane-bound, long soluble, short form. Here, we have analyzed the physiological role of Opa1 processing by generating mouse lines expressing only one cleavable isoform or non-cleavable variant thereof. Our results show that expression single preserves embryonic development health adult mice. dispensable under thermal but prolongs life span protects against mitochondrial cardiomyopathy OXPHOS-deficient Cox10 −/− Mechanistically, loss disturbs balance between biogenesis mitophagy, suppressing cardiac hypertrophic growth hearts. highlight critical regulatory processing, dynamics, metabolism for hypertrophy.

Language: Английский

Citations

5
Mitochondrial membrane potential and oxidative stress interact to regulate Oma1‐dependent processing of Opa1 and mitochondrial dynamics DOI Creative Commons
Garrett M. Fogo,

Sarita Raghunayakula,

Katlynn J. Emaus

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(18)

Published: Sept. 23, 2024

Mitochondrial form and function are regulated by the opposing forces of mitochondrial dynamics: fission fusion. dynamics highly active consequential during neuronal ischemia/reperfusion (I/R) injury. fusion is executed at inner membrane Opa1. The balance long (L-Opa1) proteolytically cleaved short (S-Opa1) isoforms critical for efficient Oma1 predominant stress-responsive protease Opa1 processing. In cell models, we assessed regulation stress. an immortalized mouse hippocampal neuron line (HT22), was sensitive to potential depolarization (rotenone, FCCP) hyperpolarization (oligomycin). Further, oxidative stress sufficient increase activity necessary depolarization-induced proteolysis. We generated knockout (KO) HT22 cells that displayed normal morphology capabilities. FCCP-induced fragmentation exacerbated in KO cells. However, were better equipped perform restorative after fragmentation, presumably due preserved L-Opa1. extended our investigations a combinatorial oxygen-glucose deprivation reoxygenation (OGD/R), where found processing activation initiated OGD ROS-dependent manner. These findings highlight novel dependence on response depolarization. demonstrate contrasting fission/fusion roles acute recovery stages Collectively, results add intersectionality nuance previously proposed models activity.

Language: Английский

Citations

5
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology DOI Creative Commons
Franziska Roth‐Walter, Ian M. Adcock, Cristina Benito‐Villalvilla

et al.

Allergy, Journal Year: 2023, Volume and Issue: 79(5), P. 1089 - 1122

Published: Dec. 18, 2023

Abstract The accumulation of senescent cells drives inflammaging and increases morbidity chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy substrates for proliferation, differentiation, activation. Metabolic imposed by environmental stress inflammation on immune tissue microenvironment thus chiefly involved the pathophysiology allergic other immune‐driven Altered is also a hallmark senescence, condition characterized loss proliferative activity remain metabolically active. Accelerated senescence can be triggered acute or responses. In contrast, replicative occurs as part physiological aging process has protective roles cancer surveillance wound healing. Importantly, change hamper response to diverse therapeutic treatments. Understanding metabolic pathways structural therefore critical detect, prevent, revert detrimental aspects senescence‐related immunopathology, developing specific diagnostics targeted therapies. this paper, we review main alterations occurring (macrophages, B cells, T cells). Subsequently, present footprints described translational studies patients with asthma obstructive pulmonary disease (COPD), ongoing preclinical clinical trials approaches aiming at targeting antagonize pathological senescence. Because recently emerging field allergy immunology, better understanding profile complex landscape needed. progress achieved so far already providing opportunities new therapies, well strategies aimed prevention supporting healthy aging.

Language: Английский

Citations

12
Characterization of isolated human astrocytes from aging brain DOI Creative Commons
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

ABSTRACT Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain’s internal milieu eventually impact neuronal function leads neurodegeneration. Until now most of evidence astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture or cell cultures derived animal models lines. In this study we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s (ADD) progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Language: Английский

Citations

0
Mitochondrial proteostasis and cellular health: insights from chaperones and autophagy DOI Open Access

Yuvraj Anandrao Jagtap,

Akash Choudhary,

Sumit Kinger

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Mitochondria are a cell's powerhouse and also have vital part in cellular processes. The emerging role of mitochondria several crucial processes highlights their physiological importance. Mitochondrial homeostasis mechanisms, including proteostasis pathways, for mitochondrial health. Failure these has an important establishment numerous complex disease conditions, such as neurodegeneration imperfect ageing. However, details impairments contribution to the pathology poorly understood. This review systematically discusses involvement mechanisms rejuvenating health fitness. We focus on various protein quality control essential how failure leads functional disturbances observed conditions. discuss recent findings based mitostasis-associated chaperones, mitoproteases, autophagy responses, which can lead emergence new possible therapeutic interventions against diseases.

Language: Английский

Citations

0
Characterization of Isolated Human Astrocytes from Aging Brain DOI Open Access
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3416 - 3416

Published: April 5, 2025

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain's internal milieu eventually impact neuronal function lead neurodegeneration. Until now, most evidence of astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived animal models lines. In this study, we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's (ADD), progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Language: Английский

Citations

0
Melatonin Rescues Influenza A Virus–Induced Cellular Energy Exhaustion via OMA1‐OPA1‐S in Acute Exacerbation of COPD DOI
Yuanyuan Wei, Jingjing Ye, Dawei Zhang

et al.

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(5)

Published: July 22, 2024

ABSTRACT Although rapid progression and a poor prognosis in influenza A virus (IAV) infection–induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms rescue strategies remain unknown. We herein demonstrated that level resting expenditure increased significantly IAV‐induced AECOPD patients cellular exhaustion emerged earlier more IAV‐infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much ATP exhaustion, severe mitochondrial structural destruction dysfunction, OXPHOS impairment IAV‐inoculated pDHBE cells, these changes rescued by melatonin. OMA1‐dependent cleavage OPA1 inner membrane shift metabolism from to glycolysis cells; however, OMA1 ‐siRNA or melatonin further treatment. Collectively, our data revealed IAV–induced via OMA1‐OPA1‐S improve clinical COPD. This treatment may serve as potential therapeutic agent for which is induced IAV.

Language: Английский

Citations

2
Targeting complement C3a receptor resolves mitochondrial hyperfusion and subretinal microglial activation in progranulin-deficient frontotemporal dementia DOI Open Access
Li Xuan Tan, Frederike Cosima Oertel,

An Cheng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Mutations in progranulin (

Language: Английский

Citations

1