scholarly journals Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3003
Author(s):  
Yun Haeng Lee ◽  
Ji Yun Park ◽  
Haneur Lee ◽  
Eun Seon Song ◽  
Myeong Uk Kuk ◽  
...  
Keyword(s):  
Energy Source ◽  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Reactive Oxygen ◽  
Mitochondrial Metabolism ◽  
Metabolic Reprogramming ◽  
Oxygen Species ◽  
Metabolic Alterations ◽  
Age Related

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases. In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.

Mitochondrial metabolism, reactive oxygen species, and macrophage function-fishing for insights

2014 ◽  
Vol 92 (11) ◽  
pp. 1119-1128 ◽  
Author(s):  
Christopher J. Hall ◽  
Leslie E. Sanderson ◽  
Kathryn E. Crosier ◽  
Philip S. Crosier
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Mitochondrial Metabolism ◽  
Oxygen Species ◽  
Macrophage Function

scholarly journals Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism

2020 ◽  
Vol 117 (18) ◽  
pp. 9964-9972 ◽  
Author(s):  
Di Yu ◽  
Yang Liu ◽  
Yiqiang Zhou ◽  
Victor Ruiz-Rodado ◽  
Mioara Larion ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
De Novo ◽  
Synthetic Lethality ◽  
Reactive Oxygen ◽  
Metabolic Reprogramming ◽  
Glutathione Metabolism ◽  
Oxygen Species ◽  
Genetic Abnormality

Isocitrate dehydrogenase (IDH) mutation is a common genetic abnormality in human malignancies characterized by remarkable metabolic reprogramming. Our present study demonstrated that IDH1-mutated cells showed elevated levels of reactive oxygen species and higher demands on Nrf2-guided glutathione de novo synthesis. Our findings showed that triptolide, a diterpenoid epoxide from Tripterygium wilfordii, served as a potent Nrf2 inhibitor, which exhibited selective cytotoxicity to patient-derived IDH1-mutated glioma cells in vitro and in vivo. Mechanistically, triptolide compromised the expression of GCLC, GCLM, and SLC7A11, which disrupted glutathione metabolism and established synthetic lethality with reactive oxygen species derived from IDH1 mutant neomorphic activity. Our findings highlight triptolide as a valuable therapeutic approach for IDH1-mutated malignancies by targeting the Nrf2-driven glutathione synthesis pathway.

scholarly journals Trolox-Sensitive Reactive Oxygen Species Regulate Mitochondrial Morphology, Oxidative Phosphorylation and Cytosolic Calcium Handling in Healthy Cells

2012 ◽  
Vol 17 (12) ◽  
pp. 1657-1669 ◽  
Author(s):  
Felix Distelmaier ◽  
Federica Valsecchi ◽  
Marleen Forkink ◽  
Sjenet van Emst-de Vries ◽  
Herman G. Swarts ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Reactive Oxygen ◽  
Cytosolic Calcium ◽  
Calcium Handling ◽  
Mitochondrial Morphology ◽  
Oxygen Species

scholarly journals Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

2016 ◽  
Vol 371 (1700) ◽  
pp. 20150434 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Reactive Oxygen Species ◽  
Vitamin D ◽  
Neuronal Cell Death ◽  
Memory Loss ◽  
Neuronal Cell ◽  
Reactive Oxygen ◽  
Cardiac Cells ◽  
Amyloid Formation ◽  
Oxygen Species ◽  
Age Related

Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca 2+ and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca 2+ and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca 2+ transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca 2+ landscape that initiates amyloid formation, which then elevates the resting level of Ca 2+ to drive the memory loss that progresses to neuronal cell death and dementia. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

Mitochondrial-derived reactive oxygen species influence ADP sensitivity, but not CPT-I substrate sensitivity

2018 ◽  
Vol 475 (18) ◽  
pp. 2997-3008 ◽  
Author(s):  
Pierre-Andre Barbeau ◽  
Paula M. Miotto ◽  
Graham P. Holloway
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Phosphorylation ◽  
Acute Exercise ◽  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Emission Rates ◽  
Mitochondrial Ros ◽  
Cpt I

The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined; however, key mitochondrial proteins, including carnitine palmitoyltransferase-I (CPT-I) and adenine nucleotide translocase, have redox-sensitive sites. Interestingly, muscle contraction has recently been shown to increase mitochondrial membrane potential and reactive oxygen species (ROS) production; therefore, we aimed to determine if mitochondrial-derived ROS influences bioenergetic responses to exercise. Specifically, we examined the influence of acute exercise on mitochondrial bioenergetics in WT (wild type) and transgenic mice (MCAT, mitochondrial-targeted catalase transgenic) possessing attenuated mitochondrial ROS. We found that ablating mitochondrial ROS did not alter palmitoyl-CoA (P-CoA) respiratory kinetics or influence the exercise-mediated reductions in malonyl CoA sensitivity, suggesting that mitochondrial ROS does not regulate CPT-I. In contrast, while mitochondrial protein content, maximal coupled respiration, and ADP (adenosine diphosphate) sensitivity in resting muscle were unchanged in the absence of mitochondrial ROS, exercise increased the apparent ADP Km (decreased ADP sensitivity) ∼30% only in WT mice. Moreover, while the presence of P-CoA decreased ADP sensitivity, it did not influence the basic response to exercise, as the apparent ADP Km was increased only in the presence of mitochondrial ROS. This basic pattern was also mirrored in the ability of ADP to suppress mitochondrial H2O2 emission rates, as exercise decreased the suppression of H2O2 only in WT mice. Altogether, these data demonstrate that while exercise-induced mitochondrial-derived ROS does not influence CPT-I substrate sensitivity, it inhibits ADP sensitivity independent of P-CoA. These data implicate mitochondrial redox signaling as a regulator of oxidative phosphorylation.

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