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Review
. 2015 Nov;1847(11):1387-400.
doi: 10.1016/j.bbabio.2015.05.021. Epub 2015 Jun 4.

The role of mitochondrial dysfunction in age-related diseases

Rebecca K Lane  1 , Tyler Hilsabeck  2 , Shane L Rea  3
Affiliations
Review

The role of mitochondrial dysfunction in age-related diseases

Rebecca K Lane et al. Biochim Biophys Acta. 2015 Nov.

Abstract

The aging process is accompanied by the onset of disease and a general decline in wellness. Insights into the aging process have revealed a number of cellular hallmarks of aging, among these epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and stem cell exhaustion. Mitochondrial dysfunction increasingly appears to be a common factor connecting several of these hallmarks, driving the aging process and afflicting tissues throughout the body. Recent research has uncovered a much more complex involvement of mitochondria in the cell than has previously been appreciated and revealed novel ways in which mitochondrial defects feed into disease pathology. In this review we evaluate ways in which problems in mitochondria contribute to disease beyond the well-known mechanisms of oxidative stress and bioenergetic deficits, and we predict the direction that mitochondrial disease research will take in years to come.

Keywords: Aging; Atherosclerosis; Immunity; Mitochondria; Neurodegeneration; Osteoporosis; Sirtuins; Stem cells.

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Figures

Figure 1.
Figure 1.. ROS as determinants of stem cell differentiation.
Depending on concentration, ROS can either cause a stem cell to differentiate, or guide it into a senescent state.
Figure 1.
Figure 1.. ROS as determinants of stem cell differentiation.
Depending on concentration, ROS can either cause a stem cell to differentiate, or guide it into a senescent state.
Figure 2.
Figure 2.. Metabolic reprogramming of differentiating stem cells.
A. In undifferentiated pluripotent stem cells, UCP2 is activated by phosphatidylinositol phosphates (PIPs) at the inner mitochondrial membrane (IMM), which prevents entry of pyruvate into the TCA cycle. Glucose is consequently shunted into alternate metabolic pathways such as the pentose phosphate pathway (PPP). B. During differentiation, the mitochondrial phosphatase PTPMT1 dephosphorylates PIPs, downregulating UCP2 and allowing pyruvate to be metabolized by the TCA cycle to fuel OXPHOS.
See this image and copyright information in PMC

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