bims-midbra 2022-03-06 papers

Issue of 2022‒03‒06
two papers selected by
Ana Paula Mendonça
University of Padova

Oxid Med Cell Longev. 2022 ;2022 3644318

Nrf2 Deficiency Attenuates Testosterone Efficiency in Ameliorating Mitochondrial Function of the Substantia Nigra in Aged Male Mice.

Baoliang Ren, Tianyun Zhang, Qiqing Guo, Jing Che, Yunxiao Kang, Rui Cui, Yu Wang, Xiaoming Ji, Guoliang Zhang, Geming Shi.

Reduced testosterone level is a common feature of aging in men. Aging, as a risk factor for several neurodegenerative disorders, shows declined mitochondrial function and downregulated mitochondrial biogenesis and mitochondrial dynamics. Mitochondrial biogenesis and mitochondrial dynamics are crucial in maintaining proper mitochondrial function. Supplementation with testosterone is conducive to improving mitochondrial function of males during aging. Nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of redox homeostasis, is involved in the ameliorative effects of testosterone supplementation upon aging. To explore Nrf2 role in the effects of testosterone supplementation on mitochondrial function during aging, we studied the efficiency of testosterone supplementation in improving mitochondrial function of Nrf2 knockout- (KO-) aged male mice by analyzing the changes of mitochondrial biogenesis and mitochondrial dynamics. It was found that wild-type- (WT-) aged male mice showed low mitochondrial function and expression levels of PGC-1α, NRF-1\NRF-2, and TFAM regulating mitochondrial biogenesis, as well as Drp1, Mfn1, and OPA1 controlling mitochondrial dynamics in the substantia nigra (SN). Nrf2 KO aggravated the defects above in SN of aged male mice. Testosterone supplementation to WT-aged male mice significantly ameliorated mitochondrial function and upregulated mitochondrial biogenesis and mitochondrial dynamics, which were not shown in Nrf2 KO-aged male mice due to Nrf2 deficiency. Testosterone deficiency by gonadectomy (GDX) decreased mitochondrial function, downregulated mitochondrial biogenesis, and altered mitochondrial dynamics balance in young male mice. Supplementation with testosterone to Nrf2 KO-GDX mice only ameliorated the alterations above but did not reverse them to sham level. Nrf2 deficiency attenuated testosterone efficiency in ameliorating mitochondrial function in the SN of aged male mice through mitochondrial biogenesis and mitochondrial dynamics to some extent. Activation of Nrf2 might contribute to testosterone-upregulating mitochondrial biogenesis and mitochondrial dynamics in the SN during aging to produce efficient mitochondria for ATP production.

DOI: https://doi.org/10.1155/2022/3644318

Rev Neurosci. 2022 Feb 28.

Understanding mitochondria and the utility of optimization as a canonical framework for identifying and modeling mitochondrial pathways.

Haym Benaroya.

The goal of this paper is to provide an overview of our current understanding of mitochondrial function as a framework to motivate the hypothesis that mitochondrial behavior is governed by optimization principles that are constrained by the laws of the physical and biological sciences. Then, mathematical optimization tools can generally be useful to model some of these processes under reasonable assumptions and limitations. We are specifically interested in optimizations via variational methods, which are briefly summarized. Within such an optimization framework, we suggest that the numerous mechanical instigators of cell and intracellular functioning can be modeled utilizing some of the principles of mechanics that govern engineered systems, as well as by the frequently observed feedback and feedforward mechanisms that coordinate the multitude of processes within cells. These mechanical aspects would need to be coupled to governing biochemical rules. Of course, biological systems are significantly more complex than engineered systems, and require considerably more experimentation to ascertain and characterize parameters and subsequent behavior. That complexity requires well-defined limitations and assumptions for any derived models. Optimality is being motivated as a framework to help us understand how cellular decisions are made, especially those that transition between physiological behaviors and dysfunctions along pathophysiological pathways. We elaborate on our interpretation of optimality and cellular decision making within the body of this paper, as we revisit these ideas in the numerous different contexts of mitochondrial functions.

Keywords: cristae morphology; energetics; mitochondria; optimization; variational mechanics

DOI: https://doi.org/10.1515/revneuro-2021-0138