Mitochondria, Oxidants, and Aging

Balaban, Robert S.; Nemoto, Shino; Finkel, Toren

doi:10.1016/j.cell.2005.02.001

Cited by 3,915 publications

(3,055 citation statements)

References 106 publications

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“…We further examined mitochondrial function and structure in DS HF and Dp16 MEF. As the mitochondrial network is the main source of cellular ROS (Balaban et al, 2005) mitochondrial ROS were quantified with a radiometric biosensor (mitoHyPer) that detects peroxide intermediates in the organelle (see methods). Cellular ROS, mitochondrial membrane potential (MMP) and network integrity were also assessed to establish the putative correlation between ROS levels and mitochondrial deficits.…”

Section: Resultsmentioning

confidence: 99%

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Zamponi

Coşkun

et al. 2018

Aging Cell

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SummaryMounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2‐mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria‐targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2‐mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial‐specific interventions as a key aspect of antioxidant and antiaging therapies.

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Section: Resultsmentioning

confidence: 99%

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Zamponi

Coşkun

et al. 2018

Aging Cell

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“…In this context, an interesting relationship was found between the rate of ROS production during mitochondrial reverse electron transport in vitro and lifespan in vertebrate homeotherms (Lambert et al., 2007). Several reviews have described the mechanisms of ROS production in mitochondria and discussed their potential contribution in aging (Balaban et al., 2005; Brand, 2010). Here, we will only give a brief summary and we will focus on the possible link between ROS production and mPTP opening during aging.…”

Section: Regulating Factors Of Mptp and Agingmentioning

confidence: 99%

“…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%

“…Although a large amount of data support the role of mitochondrial ROS production in aging, other features of mitochondrial physiology and dysfunction, including the mitochondrial permeability transition, have been more recently implicated in the mechanisms of aging (Balaban, Nemoto, & Finkel, 2005; Bratic & Larsson, 2013; Gonzalez‐Freire et al., 2015; Payne & Chinnery, 2015). …”

Section: Introductionmentioning

confidence: 99%

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

2018

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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.

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“…Mitochondria, together with peroxisomes, are the major source of ROS. This metabolic role assigns to these organelles a perhaps crucial function in the determination of lifespan (see Balaban et al 39 for a review). Mitochondrial dynamics seems to play a role in production of ROS as well as in longevity.…”

Section: Function Follows Form: Consequences Of Mitochondrial Shape Cmentioning

confidence: 99%

A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

Scorrano

2007

Cell Death Differ

132

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Mitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release is accompanied by fragmentation of the mitochondrial reticulum and by remodelling of the internal structure of the organelle. Here we review data supporting the existence of a regulatory network in the inner mitochondrial membrane that includes optic atrophy 1 (Opa1), a dynamin-related protein, and presenilin-associated rhomboidlike (Parl), a rhomboid protease. Opa1 regulates remodelling of the cristae independent of its effect on fusion. Cristae remodelling conversely requires Parl, which participates in the production of a soluble form of Opa1 retrieved together with the integral membrane one in oligomers that are disrupted early during apoptosis. Parl itself is regulated by proteolysis to generate a cleaved form, which in turn modulates the shape of the mitochondrial reticulum. Cleavage of Parl depends on its phosphorylation state around the cleavage site, implicating mitochondrial kinases and phosphatases in the regulation of mitochondrial shape.

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Mitochondria, Oxidants, and Aging

Cited by 3,915 publications

References 106 publications

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

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

A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

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