Influence of aging on membrane permeability transition in brain mitochondria

Toman, J; Fiskum, Gary

doi:10.1007/s10863-011-9337-8

Cited by 64 publications

(34 citation statements)

References 59 publications

(93 reference statements)

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“…P. anserina cultures have been found to die by mPTP-induced apoptosis (24), and the mPTPC also seems to be involved in mammalian aging. Mitochondria in the brain of aged rodents are more sensitive to Ca 2+ -induced permeability transition compared with the young mature rodent brain (25).…”

mentioning

confidence: 93%

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

Daum

Walter

Horst

et al. 2013

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

213

195

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Aging is one of the most fundamental, yet least understood biological processes that affect all forms of eukaryotic life. Mitochondria are intimately involved in aging, but the underlying molecular mechanisms are largely unknown. Electron cryotomography of whole mitochondria from the aging model organism Podospora anserina revealed profound age-dependent changes in membrane architecture. With increasing age, the typical cristae disappear and the inner membrane vesiculates. The ATP synthase dimers that form rows at the cristae tips dissociate into monomers in inner-membrane vesicles, and the membrane curvature at the ATP synthase inverts. Dissociation of the ATP synthase dimer may involve the peptidyl prolyl isomerase cyclophilin D. Finally, the outer membrane ruptures near large contact-site complexes, releasing apoptogens into the cytoplasm. Inner-membrane vesiculation and dissociation of ATP synthase dimers would impair the ability of mitochondria to supply the cell with sufficient ATP to maintain essential cellular functions.subtomogram averaging | cell death

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mentioning

confidence: 93%

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

Daum

Walter

Horst

et al. 2013

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

213

195

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“…Two opening states of the pore have been distinguished, a permanent or long‐lasting state which is associated with cell death, and a transient opening state having a physiological role by providing a pathway to release ROS and calcium from mitochondria which is also regulated by CypD (Elrod et al., 2010; Hausenloy, Wynne, Duchen, & Yellon, 2004; Petronilli et al., 1999). The mPTP is now considered to be central in numerous conditions such as heart, brain, or liver ischemia–reperfusion (Friberg & Wieloch, 2002; Halestrap, 2010; Kim, He, Qian, & Lemasters, 2003; Morin, Hauet, Spedding, & Tillement, 2001; Rauen & de Groot, 2004), drug‐induced liver injury (Jaeschke, McGill, & Ramachandran, 2012), age‐related neurodegenerative diseases (Rao, Carlson, & Yan, 2014), and accumulating data imply the mPTP in organ dysfunction occurring during aging (Hepple, 2016; Rocha‐Rodrigues et al., 2013; Toman & Fiskum, 2011). Conversely, caloric restriction, which is a proven strategy to delay aging and age‐related disease (Balasubramanian, Howell, & Anderson, 2017), is associated with the inhibition of mPTP opening (Amigo, Menezes‐Filho, Luévano‐Martínez, Chausse, & Kowaltowski, 2017; Hofer et al., 2009; Kristal & Yu, 1998; Menezes‐Filho et al., 2017).…”

Section: Introductionmentioning

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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“…Apart from their contribution to the aetiology of diseases, mitochondria have also been considered to be involved in aging (Crompton, 2004;Toman and Fiskum, 2011). Relevant to this, aging studies in the human and murine brain resulted in the identification of "aging markers" that concern gene expression and DNA damage.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Cyclophilin D regulates lifespan and protein expression of aging markers in the brain of mice

et al. 2017

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Cyclophilin D (cypD) modulates the properties of the permeability transition pore, a phenomenon implicated in the manifestation of many diseases including aging. Here, we examined the effects of partial or complete deletion of cypD on i) lifespan, ii) forebrain protein expression of 18 aging markers as well as regional expression of GFAP, mGluR1, and alpha-synuclein, and iii) behaviour of aged (> 24 month) male and female mice. Both male and female cypD heterozygous but not KO mice exhibited increased lifespans compared to WT littermates, associated with alterations in the protein expression of some markers, albeit without exhibiting changes in behaviour.

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Influence of aging on membrane permeability transition in brain mitochondria

Cited by 64 publications

References 59 publications

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

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

Cyclophilin D regulates lifespan and protein expression of aging markers in the brain of mice

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