6 research outputs found
Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program.
The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is electrophoretically transported by the ATP/ADP antiporter to the catalytic site of bound hexokinase or bound creatine kinase without ATP dilution in the cytosol. One of the kinase reaction products, ADP, is transported back to the mitochondrial matrix via the antiporter, again through an electrophoretic process without cytosol dilution. The system in question continuously supports H <sup>+</sup> -ATP synthase with ADP until glucose or creatine is available. Under these conditions, the membrane potential, ∆ψ, is maintained at a lower than maximal level (i.e., mild depolarization of mitochondria). This ∆ψ decrease is sufficient to completely inhibit mROS generation. In 2.5-y-old mice, mild depolarization disappears in the skeletal muscles, diaphragm, heart, spleen, and brain and partially in the lung and kidney. This age-dependent decrease in the levels of bound kinases is not observed in NMRs and bats for many years. As a result, ROS-mediated protein damage, which is substantial during the aging of short-lived mice, is stabilized at low levels during the aging of long-lived NMRs and bats. It is suggested that this mitochondrial mild depolarization is a crucial component of the mitochondrial anti-aging system
Transcription Factor Nrf2 as a Potential Therapeutic Target for Prevention of Cytokine Storm in COVID-19 Patients
Abstract: Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation – the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients. © 2020, Pleiades Publishing, Ltd
Age-associated murine cardiac lesions are attenuated by the mitochondria-targeted antioxidant SkQ1
Age-related changes in mammalian hearts
often result in cardiac hypertrophy and fibrosis that are
preceded by inflammatory infiltration. In this paper, we
show that lifelong treatment of BALB/c and C57BL/6
mice with the mitochondria-targeted antioxidant SkQ1
retards senescence-associated myocardial disease
(cardiomyopathy), cardiac hypertrophy, and diffuse
myocardial fibrosis. To investigate the molecular basis
of the action of SkQ1, we have applied DNA microarray
analysis. The global gene expression profile in heart
tissues was not significantly affected by administration
of SkQ1. However, we found some small but statistically
significant modifications of the pathways related to cellto-cell contact, adhesion, and leukocyte infiltration.
Probably, SkQ1-induced decrease in leukocyte and
mesenchymal cell adhesion and/or infiltration lead to a
reduction in age-related inflammation and subsequent
fibrosis. The data indicate a causative role of
mitochondrial reactive oxygen species in cardiovascular
aging and imply that SkQ1 has poteential as a drug
against age-related cardiac dysfunction