Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex

Frenzel, Monika; Rommelspacher, Hans; Sugawa, M.; Dencher, Norbert A.

doi:10.1016/j.exger.2010.02.003

Cited by 118 publications

(84 citation statements)

References 72 publications

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“…This brain area depends considerably on mitochondrial functionality as documented by the large number of papers describing agerelated mitochondrial dysfunctions such as decreased rate of electron transfer in complex I and complex IV, decreased membrane potential, and increased content of macromolecular oxidized products (Bagh et al 2011;Frenzel et al 2010;Gilmer et al 2010;Guevara et al 2009Guevara et al , 2011Navarro and Boveris 2010;Navarro et al 2008). In this brain area, we found that AL rats presented an age-related increase in TFAM amount, which was not associated with an increase in mtDNA content, but with a mtDNA decrease.…”

Section: Discussionmentioning

confidence: 49%

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

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Fracasso

Pesce

et al. 2012

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Aging markedly affects mitochondrial biogenesis and functions particularly in tissues highly dependent on the organelle's bioenergetics capability such as the brain's frontal cortex. Calorie restriction (CR) diet is, so far, the only intervention able to delay or prevent the onset of several age-related alterations in different organisms. We determined the contents of mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), and the 4.8-kb mtDNA deletion in the frontal cortex from young (6-monthold) and aged (26-month-old), ad libitum-fed (AL) and calorie-restricted (CR), rats. We found a 70 % increase in TFAM amount, a 25 % loss in mtDNA content, and a 35 % increase in the 4.8-kb deletion content in the aged AL animals with respect to the young rats. TFAM-specific binding to six mtDNA regions was analyzed by mtDNA immunoprecipitation and semiquantitative polymerase chain reaction (PCR), showing a marked age-related decrease. Quantitative realtime PCR at two subregions involved in mtDNA replication demonstrated, in aged AL rats, a remarkable decrease (60-70 %) of TFAM-bound mtDNA. The decreased TFAM binding is a novel finding that may explain the mtDNA loss in spite of the compensatory TFAM increased amount. In aged CR rats, TFAM amount increased and mtDNA content decreased with respect to young rats' values, but the extent of the changes was smaller than in aged AL rats. Attenuation of the age-related effects due to the diet in the CR animals was further evidenced by the unchanged content of the 4.8-kb deletion with respect to that of young animals and by the partial prevention of the age-related decrease in TFAM binding to mtDNA.

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Section: Discussionmentioning

confidence: 49%

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

Picca

Fracasso

Pesce

et al. 2012

AGE

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“…This view is also supported by the observation that mtRNA remains localized at the nucleoids where it was synthesized (35). Furthermore, recent evidence indicates that the respiration complexes are not found as monomers, but are organized in supercomplexes (36)(37)(38) and even respiratory strings (39). Such an arrangement not only speeds up the enzyme kinetics by substrate channeling, but also connects mtDNA to its gene products.…”

Section: Combating the Accumulation Of Mitochondrial Mutantsmentioning

confidence: 99%

“…Such an arrangement not only speeds up the enzyme kinetics by substrate channeling, but also connects mtDNA to its gene products. It has been shown that supercomplexes contain members of all respiratory complexes encoded by mtDNA, i.e., I, III, and IV (37,38). Thus, if mtDNA is attached to one of the complexes, a link to all of them exists.…”

Section: Combating the Accumulation Of Mitochondrial Mutantsmentioning

confidence: 99%

Evolution of the mitochondrial fusion–fission cycle and its role in aging

Kowald

Kirkwood

2011

Proc. Natl. Acad. Sci. U.S.A.

120

109

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Mitochondria are organelles of eukaryotic cells that contain their own genetic material and evolved from prokaryotic ancestors some 2 billion years ago. They are the main source of the cell's energy supply and are involved in such important processes as apoptosis, mitochondrial diseases, and aging. During recent years it also became apparent that mitochondria display a complex dynamical behavior of fission and fusion, the function of which is as yet unknown. In this paper we develop a concise theory that explains why fusion and fission have evolved, how these processes are related to the accumulation of mitochondrial mutants during aging, why the mitochondrial DNA has to be located close to the respiration complexes where most radicals are generated, and what selection pressures shaped the slightly different structure of animal and plant mitochondria. We believe that this “organelle control” theory will help in understanding key processes involved in the evolution of the mitochondrial genome and the aging process.

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“…Aging was shown to alter some properties of ATP synthase (Frenzel, Rommelspacher, Sugawa, & Dencher, 2010). Aging could decrease the maximal ATP synthase activity and impact the available ATP concentration in vivo but can also contribute to mPTP activation.…”

Section: Putative Molecular Components Of Mptp and Agingmentioning

confidence: 99%

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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Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex

Cited by 118 publications

References 72 publications

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

Evolution of the mitochondrial fusion–fission cycle and its role in aging

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

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