Mitochondrial fusion, fission, and mitochondrial toxicity

Toxicology, Год журнала: 2017, Номер 391, С. 42 - 53

Опубликована: Авг. 5, 2017

Язык: Английский

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Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia–reperfusion injury

Acta Pharmaceutica Sinica B, Год журнала: 2020, Номер 10(10), С. 1866 - 1879

Опубликована: Апрель 9, 2020

Mitochondrial damage is a critical contributor to cardiac ischemia/reperfusion (I/R) injury. quality control (MQC) mechanisms, series of adaptive responses that preserve mitochondrial structure and function, ensure cardiomyocyte survival function after I/R MQC includes fission, fusion, mitophagy mitochondria-dependent cell death. The interplay among these linked pathological changes such as redox imbalance, calcium overload, energy metabolism disorder, signal transduction arrest, the unfolded protein response endoplasmic reticulum stress. Excessive fission an early marker Reduced fusion has been observed in stressed cardiomyocytes correlates with dysfunction depression. Mitophagy allows autophagosomes selectively degrade poorly structured mitochondria, thus maintaining network fitness. Nevertheless, abnormal maladaptive Although mitochondria serve fuel source heart by continuously producing adenosine triphosphate, they also stimulate death inducing apoptosis or necroptosis reperfused myocardium. Therefore, defects may determine fate cardiomyocytes. In this review, we summarize regulatory mechanisms effects myocardial injury, highlighting potential targets for clinical management reperfusion.

Язык: Английский

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Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation

npj Regenerative Medicine, Год журнала: 2020, Номер 5(1)

Опубликована: Ноя. 23, 2020

Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified central system disorders. Membrane leakage electrolyte imbalances, pro-apoptotic pathway activation, mitophagy among mechanisms implicated pathogenesis of neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's disease, well ischemic stroke. this review, we summarize pathways that contribute disease progression. Further, discuss pathological states damaged mitochondria impose on normal processes explore new therapeutic approaches diseases.

Язык: Английский

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Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology

Critical Reviews in Biochemistry and Molecular Biology, Год журнала: 2018, Номер 53(3), С. 311 - 334

Опубликована: Апрель 11, 2018

Sirtuins are NAD+-dependent protein deacylases/ADP-ribosyltransferases that have emerged as candidate targets for new therapeutics to treat metabolic disorders and other diseases, including cancer. The sirtuin SIRT5 resides primarily in the mitochondrial matrix catalyzes removal of negatively charged lysine acyl modifications; succinyl, malonyl, glutaryl groups. Evidence has now accumulated document roles a significant regulator cellular homeostasis, context- cell-type specific manner, been observed previously family members. regulates substrates involved glycolysis, TCA cycle, fatty acid oxidation, electron transport chain, ketone body formation, nitrogenous waste management, ROS detoxification, among processes. plays pivotal cardiac physiology stress responses is regulation numerous aspects myocardial energy metabolism. implicated neoplasia, both tumor promoter suppressor context-specific may serve protective function setting neurodegenerative disorders. Here, we review current understanding functional impacts on its targets, molecular functions normal pathological conditions. Finally, will discuss potential utility drug target also summarize status, progress, challenges developing small molecule compounds modulate activity with high potency specificity.

Язык: Английский

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Mitochondrial dysfunction in the development and progression of neurodegenerative diseases

Archives of Biochemistry and Biophysics, Год журнала: 2020, Номер 702, С. 108698 - 108698

Опубликована: Ноя. 28, 2020

Язык: Английский

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Mitochondrial dysfunction as a trigger of innate immune responses and inflammation

Toxicology, Год журнала: 2017, Номер 391, С. 54 - 63

Опубликована: Июль 30, 2017

Язык: Английский

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Mitochondrial dysfunction and the AKI-to-CKD transition

AJP Renal Physiology, Год журнала: 2020, Номер 319(6), С. F1105 - F1116

Опубликована: Окт. 19, 2020

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic disease (CKD). Even milder AKI adverse consequences could progress to renal fibrosis, which is ultimate common pathway various terminal diseases. Thus, it urgent develop a strategy hinder transition from CKD. Some mechanisms AKI-to-CKD have revealed, such nephron loss, cell cycle arrest, persistent inflammation, endothelial with vascular rarefaction, epigenetic changes. Previous studies elucidated pivotal role mitochondria in acute injuries demonstrated that fitness this organelle major determinant both pathogenesis recovery organ function. Recent research suggested damage mitochondrial function early crucial leading tubular insufficiency. Dysregulation homeostasis, alterations bioenergetics, stress cross talk contribute transition. In review, we focus on pathophysiology after progression CKD, confirming targeting represents potentially effective therapeutic

Язык: Английский

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Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life, Год журнала: 2021, Номер 11(4), С. 332 - 332

Опубликована: Апрель 10, 2021

Mitochondria are key intracellular organelles involved not only in the metabolic state of cell, but also several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these characterized by continuous events fission fusion which contribute to dynamic plasticity their network, strongly influenced mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount reactive oxygen species (ROS) inside eukaryotic cells, reported mediate plethora both physiological pathological growth regulation autophagy, apoptosis, metastasis. Therefore, targeting ROS could be promising strategy overcome hinder development diseases cancer, where malignant possessing higher respect healthy ones, specifically targeted therapeutic treatments. In this review, we collected ultimate findings on blended interplay among shaping, ROS, signaling pathways, order dissection molecular mechanisms pathophysiology possibly improving future approaches.

Язык: Английский

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Heat shock protein 22 modulates NRF1/TFAM-dependent mitochondrial biogenesis and DRP1-sparked mitochondrial apoptosis through AMPK-PGC1α signaling pathway to alleviate the early brain injury of subarachnoid hemorrhage in rats

Redox Biology, Год журнала: 2021, Номер 40, С. 101856 - 101856

Опубликована: Янв. 10, 2021

Mitochondrial dysfunction has been widely accepted as a detrimental factor in subarachnoid hemorrhage (SAH)-induced early brain injury (EBI), which is eminently related to poor neurologic function outcome. Previous studies have revealed that enhancement of heat shock protein 22 (hsp22) under conditions stress friendly mediator mitochondrial homeostasis, oxidative and apoptosis, thus accelerating neurological recovery. However, no study confirmed whether hsp22 attenuates apoptosis the setting SAH-induced EBI. Our results indicated endogenous hsp22, p-AMPK/AMPK, PGC1α, TFAM, Nrf1 Drp1 were significantly upregulated cortical neurons response SAH, accompanied by impairment, edema, neuronal degeneration, lower level mtDNA ATP, mitochondria-cytosol translocation cytochrome c, caspase 3-involved apoptosis. exogenous maintained function, reduced improved these effects highly dependent on PGC1α-related biogenesis/fission, evidenced co-application PGC1α siRNA. Furthermore, we demonstrated blockade AMPK with dorsomorphin also compromised neuroprotective actions along alterations its associated pathway molecules. These data exerted salvaging an AMPK-PGC1α manner, modulates TFAM/Nrf1-induced biogenesis positive feedback DRP1-triggered negative feedback, further reducing injury. Boosting repressing excessive fission mitochondria may be efficient treatment relieve SAH-elicited

Язык: Английский

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The Mitochondrial Response to DNA Damage

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Май 12, 2021

Mitochondria are double membrane organelles in eukaryotic cells that provide energy by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They crucial to many aspects of cellular metabolism. contain their own DNA encodes for essential proteins involved the execution normal mitochondrial functions. Compared with nuclear DNA, (mtDNA) is more prone be affected damaging agents, and accumulated damages may cause dysfunction drive pathogenesis a variety human diseases, including neurodegenerative disorders cancer. Therefore, understanding better how mtDNA repaired will facilitate developing therapeutic strategies. In this review, we focus on our current repair system. We also discuss other events promoted excessive inefficient repair, such as fusion, fission, mitophagy, which serve quality control clearing damaged mtDNA.

Язык: Английский

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