From mitochondria to cells to humans: Targeting bioenergetics in aging and disease

Berry, Brandon J.; Pharaoh, Gavin; Marcinek, David J.

doi:10.1016/j.biocel.2023.106391

Cited by 3 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there is no evidence that the mitochondria of old cells are uncoupled. Alternatively, it was suggested that the lower ∆Ψm in aging is a result of an aging-specific metabolic state that impairs bioenergetic functions, and that this leads to disease and a shortened lifespan [23][24][25][26][27]. However, it was not specified what exactly this metabolic state is and how aging leads to this state.…”

Section: Discussionmentioning

confidence: 99%

“…Another often reported mitochondrial dysfunction in aging is reduction in the magnitude of ∆Ψm (reviewed in [21][22][23]. It was recently suggested that the reduction in ∆Ψm in aged animals is a major cause of aging [23][24][25][26][27]-this claim was supported by the demonstration that the optogenetic-induced increase of ∆Ψm increased C. elegans lifespan [25]-and that calorie restriction that increases C. elegans lifespan restores ∆Ψm in aged animals [26]. In animal cells ∆Ψm varies within a narrow range (−130 to −180 mV); many metabolic functions affect the magnitude of ∆Ψm.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore

Rottenberg

2023

IJMS

View full text Add to dashboard Cite

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here, I critically review studies that reported reduction in ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial permeability transition pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and to retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial unfolded protein response by reduction in ∆Ψm and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as resulting from activation or inhibition of the voltage-gated mPTP, respectively.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore

Rottenberg

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…However, there is no evidence that mitochondria of old cells are uncoupled. Alternatively, it was suggested that the lower ∆Ψm in aging is a result of aging-specific metabolic state that impair bioenergetic functions and that this leads to disease and shorten lifespan [23][24][25][26][27]. However, it was not specified what exactly is this metabolic state and how does aging leads to this state.…”

Section: Discussionmentioning

confidence: 99%

“…Another often reported mitochondrial dysfunction in aging is the reduction in the magnitude of ∆Ψm (reviewed in [21][22][23]. It was recently suggested that the reduction of ∆Ψm in aged animal is a major cause of aging [23][24][25][26][27] and this claim was supported by the demonstration that the optogenetic induced increase of ∆Ψm increased C. elegans lifespan [25] and that calorie restriction, that increases C. elegans lifespan, restore ∆Ψm in aged animals [26]. In animal cells ∆Ψm varies within relatively narrow range (130 -180 mV) and many metabolic functions affect the magnitude of ∆Ψm.…”

Section: Introductionmentioning

confidence: 99%

The Reduction of Mitochondrial Membrane Potential in Aging: The Role of the Mitochondria Permeability Transition Pore

Rottenberg¹

2023

Preprint

View full text Add to dashboard Cite

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial Permeability Transition Pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.

show abstract

“…At the core of this intricate system lies the mitochondria that plays a pivotal role in energy production, sensing, adapting, and responding to the cellular energy demands. Mitochondria are the primary sites of cellular respiration, where the process of oxidative phosphorylation (OXPHOS) converts nutrients into adenosine triphosphate (ATP) [7][8][9][10] . Redox cofactors, the oxidized (NAD + ) and reduced (NADH) forms of nicotinamide, act as "fuel" for the mitochondria [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

High-energy demand and nutrient exhaustion in MTCH2 knockout cells

Chourasia,

Petucci,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection from diet-induced obesity. We now show using temporal metabolomics that MTCH2 deletion results in a high ATP demand, an oxidized environment, a high lipid/amino acid/carbohydrate metabolism, and in the decrease of many metabolites. Lipidomics analyses show a strategic adaptive decrease in membrane lipids and an increase in storage lipids in MTCH2 knockout cells. Importantly, all the metabolic changes in the MTCH2 knockout cells were rescued by MTCH2 re-expression. Interestingly, this imbalance in energy metabolism and reductive potential triggered by MTCH2-deletion inhibits adipocyte differentiation, an energy consuming reductive biosynthetic process. In summary, loss of MTCH2 results in an increase in energy demand that triggers a catabolic and oxidizing environment, which fails to fuel the anabolic processes during adipocyte differentiation.

show abstract

From mitochondria to cells to humans: Targeting bioenergetics in aging and disease

Cited by 3 publications

References 50 publications

The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore

The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore

The Reduction of Mitochondrial Membrane Potential in Aging: The Role of the Mitochondria Permeability Transition Pore

High-energy demand and nutrient exhaustion in MTCH2 knockout cells

Contact Info

Product

Resources

About