The Impact Of Fasting In Mitochondrial Function
Mitochondria are a type of cell organelles that are responsible for the production of energy. Using sources such as carbohydrates or fatty acids, for example, from our food intake and body reserves, they contribute to their processing, transforming these molecules into compounds that our organisms can use as fuel. These molecules are called adenosine triphosphate (ATP).
Nowadays, there is a constant flux of news concerning intermittent fasting, or time-restricted feeding. This kind of approach to nutrition limits the intake of food during periods of days, in a row; or during several hours, in most of the days (14-16 hours a day of fasting are the minimum amount to achieve some beneficial effects).
Independently of the type of fasting practice, there seems to be some important connections between it and mitochondrial benefits, that may deserve some reflexion, and this is what I will try to summarize with this article.
Energy Supply By Fatty Acids
Fatty acids are the main substrate to the production of ketones (a component that is synthesized in the liver, through oxidation, when there is a low intake of carbohydrates).
Healthy people, with no specific time-restricted periods of food consumption, have ketone plasma concentrations between 0 and 0.3 mmol/L; while individuals doing that kind of diet, can have levels between 0.3 and 5 mmol/L.
When there are no carbohydrates available, as it happens with states of fast, the human body uses its fatty acids as an energy source, producing more ketones, in the liver, and turning them into sources of ATP, through transformations in extra-hepatic mitochondria.
These ketones are a source of alternative fuel, mainly in organs such as the heart and the brain, but also in the skeletal muscle.
Mitochondrial Biogenesis Stimulation
During the process of fatty acid oxidation, it is necessary, for it to happen, the intervention of Peroxisome proliferator-activated receptor Gamma Coactivator 1 (PGC-1). This means that, indirectly, fasting induces the expression of PGC-1.
PGC-1 has been linked to inducing the expression of genes responsible for encoding mitochondrial proteins that promote the transport of electrons (final step of production of ATP); for increasing the number of mitochondria available and for stimulating the development of mitochondrial DNA content.
These are the processes that lead to healthy development of mitochondria, thus mitochondrial biogenesis.
Mitochondrial Autophagy
Autophagy is a process that a cell uses to metabolize its own components: in can be non-selective, or selective (this targets specific damaged or excess organelles: damaged mitochondria, or lipid droplets, for example). In fasting states, due to shortage of ATP, there is an activation of the enzyme Adenosine Monophosphate-activated Protein Kinase (AMPK).
This enzyme, activating the Unc-51-Like Kinase 1 (ULK-1), initiates de autophagy, after inhibition of the biological “break” that usually inhibits autophagy (mammalian Target Of Rapamycin (mTOR).
In the liver, these mechanisms lead to a specific kind of autophagy: the lipophagy. Through the same mechanisms, fasting allows cells to utilize their fat reserves, getting rid of lipid droplets.
These are just some of the mechanisms that explain why mitochondria is one of the most studied organelles of the human body, in our time. Some of the assumptions here explained still need more time to be analyzed, and mainly its impact in human performance and longevity; but the increasing amount of evidence that shows the positive relation between a simple lifestyle modification such as intermittent fasting/time-restricted feeding and mitochondria health, is very promising and makes this one of the most exciting fields in today’s medicine.
31/07/2023
