The Interplay Between Respiratory Supercomplexes and ROS in Aging

Genova, Maria Luisa; Lenaz, Giorgio

doi:10.1089/ars.2014.6214

Cited by 109 publications

(88 citation statements)

References 418 publications

(392 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is feasible that increasing the removal of defective mitochondria by mitophagy can lower the levels of ROS and the resultant cellular damage and its consequences in proliferating cells driven to quiescence (58). Also, in response to mitochondrial DNA damage, mitophagy is increased in a positive loop, and we found that increasing mitophagy via TIA1 and TIAR overexpression could decrease the rates of mtDNA instability.…”

Section: Discussionmentioning

confidence: 62%

T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression

Carrascoso

Alcalde

Sánchez-Jiménez

et al. 2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

Mitochondria undergo frequent morphological changes to control their function. We show here that T-cell intracellular antigens (TIA1b/TIARb) and Hu antigen R (HuR) have antagonistic roles in mitochondrial function by modulating the expression of mitochondrial shaping proteins. Expression of TIA1b/TIARb alters the mitochondrial dynamic network by enhancing fission and clustering, which is accompanied by a decrease in respiration. In contrast, HuR expression promotes fusion and cristae remodeling and increases respiratory activity. Mechanistically, TIA proteins downregulate the expression of optic atrophy 1 (OPA1) protein via switching of the splicing patterns of OPA1 to facilitate the production of OPA1 variant 5 (OPA1v5). Conversely, HuR enhances the expression of OPA1 mRNA isoforms through increasing steady-state levels and targeting translational efficiency at the 3= untranslated region. Knockdown of TIA1/ TIAR or HuR partially reversed the expression profile of OPA1, whereas knockdown of OPA1 or overexpression of OPA1v5 provoked mitochondrial clustering. Middle-term expression of TIA1b/TIARb triggers reactive oxygen species production and mitochondrial DNA damage, which is accompanied by mitophagy, autophagy, and apoptosis. In contrast, HuR expression promotes mitochondrion-dependent cell proliferation. Collectively, these results provide molecular insights into the antagonistic functions of TIA1b/TIARb and HuR in mitochondrial activity dynamics and suggest that their balance might contribute to mitochondrial physiopathology.

show abstract

Section: Discussionmentioning

confidence: 62%

T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression

Carrascoso

Alcalde

Sánchez-Jiménez

et al. 2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…In light of the recent finding that remodeling of the CL fatty acyl groups does not affect mitochondrial morphology or oxidative phosphorylation (109), it is unclear whether the changes in CL molecular species have an effect on the respiratory supercomplexes. Respiratory supercomplexes are thought to play a role in the enhancement of electron flow and thereby to prevent the formation of excess oxygen radicals (78,110). Thus, it is possible that the reduced level of the supercomplexes in the pah1⌬ mutant might contribute to the elevated level of superoxide.…”

Section: Discussionmentioning

confidence: 99%

Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span

Park

Han

Mileykovskaya

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Pah1 phosphatidate phosphatase regulates the synthesis of triacylglycerol and membrane phospholipids. Results: The lack of Pah1 causes increases in phospholipid synthesis, ATP consumption, and oxidative stress and a decrease in chronological life span. Conclusion: Pah1 plays a role in chronological life span by regulating lipid synthesis. Significance: Pah1-mediated regulation of triacylglycerol and phospholipid syntheses is important for chronological life span.

show abstract

“…This was assigned to the decline in the electron transfer chain capacity, the dysfunction of respiratory complexes, the decrease in ROS scavenging enzymes, and the induction of mutations of mitochondrial DNA, which is susceptible to oxidative damage because it lacks protection from ROS and because of its proximity to them (Balaban et al., 2005; Genova & Lenaz, 2015; Hoppel, Lesnefsky, Chen, & Tandler, 2017; Kwon, Choi, Cho, & Lee, 2015). It was suggested that the accumulation of these mutations in turn deteriorates electron transfer chain function and further increases ROS production, leading to a deleterious vicious cycle.…”

Section: Regulating Factors Of Mptp and Agingmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

View full text Add to dashboard Cite

SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

show abstract

The Interplay Between Respiratory Supercomplexes and ROS in Aging

Abstract: A better understanding on the forces affecting SC association would allow the manipulation of ROS generation, directing these species to their physiological signaling role.

Cited by 109 publications

References 418 publications

T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression

T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression

Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span

Mitochondria and aging: A role for the mitochondrial transition pore?

Contact Info

Product

Resources

About