Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Abstract

Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

“…This review, similar to a previous review on mitochondria [ 7 ], starts with evolution of this phenomenon on earth. Hormesis effects are described and explained in biochemical and molecular terms with special attention to the immune system.…”

“…It is associated with an increased risk of type 2 diabetes mellitus (T2DM), myocardial infarction, and stroke. MetS have been estimated to affect 20–30% of adults worldwide [ 7 ]. T2DM confers an excessive risk for CVD.…”

“…Polypharmacotherapy is clinically manifested by a reduction in the effectiveness of pharmacotherapy. Perhaps, interventions that are based on dysregulated mitochondria could help to reduce multidrug usage [ 7 ].…”

“…Homeostasis describes a system of balance of a cell with respect to energy and environment. Mitochondria play an important role in maintaining homeostasis [ 7 ]. Hormesis, which should not be mixed-up with homeopathy, describes the biochemical mechanisms of a cell’s adaptation to low-dose stress.…”

“…If PERM-mediated control is offline, impaired, or dysregulated, reactive species (RCS, ROS, RNS) and stressors could have a negative effect. That seems to be the case in metabolic syndrome, degenerative disorders, chronic inflammation, and cancer [ 7 ]. Ionized calcium might play a role in maintaining the correct rhythm of PERM modulation [ 138 ].…”