Chemosphere, Journal Year: 2018, Volume and Issue: 218, P. 577 - 588
Published: Nov. 23, 2018
Language: Английский
Chemosphere, Journal Year: 2018, Volume and Issue: 218, P. 577 - 588
Published: Nov. 23, 2018
Language: Английский
Toxicology, Journal Year: 2017, Volume and Issue: 391, P. 42 - 53
Published: Aug. 5, 2017
Language: Английский
Citations
431Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 10(10), P. 1866 - 1879
Published: April 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.
Language: Английский
Citations
264npj Regenerative Medicine, Journal Year: 2020, Volume and Issue: 5(1)
Published: Nov. 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.
Language: Английский
Citations
256Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2018, Volume and Issue: 53(3), P. 311 - 334
Published: April 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.
Language: Английский
Citations
220Archives of Biochemistry and Biophysics, Journal Year: 2020, Volume and Issue: 702, P. 108698 - 108698
Published: Nov. 28, 2020
Language: Английский
Citations
197Toxicology, Journal Year: 2017, Volume and Issue: 391, P. 54 - 63
Published: July 30, 2017
Language: Английский
Citations
174AJP Renal Physiology, Journal Year: 2020, Volume and Issue: 319(6), P. F1105 - F1116
Published: Oct. 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
Language: Английский
Citations
150Life, Journal Year: 2021, Volume and Issue: 11(4), P. 332 - 332
Published: April 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.
Language: Английский
Citations
142Redox Biology, Journal Year: 2021, Volume and Issue: 40, P. 101856 - 101856
Published: Jan. 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
Language: Английский
Citations
118Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9
Published: May 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.
Language: Английский
Citations
115