They reveal how the body optimizes respiratory capacity during exercise

Mitochondria are multifunctional organelles whose dysfunction is associated with cardiovascular, inflammatory or neurodegenerative diseases and the aging process. They are the main powerhouses of cells and produce most of their energy from basic compounds such as sugars or lipids in a process known as mitochondrial respiration. One of the main causes of cell damage in mitochondrial diseases is a lack of energy, especially in tissues with greater energy dependence such as the brain, skeletal muscles, liver or heart

Now a team of researchers from the National Center for Cardiovascular Research (CNIC) in Spain, the Center for Molecular Biology Severo Ochoa (CBMSO) in Spain and the laboratory of Professor Johan Auwerx from the University of Lausanne in Switzerland have confirmed that in humans the molecular mechanism by which mitochondria adjust one of their elements , the electron transport chain (ETC), whose function is energy production, to optimize metabolism, cardiorespiratory functions and the ability to perform physical exercises.

The study was published in the academic journal Nature Metabolism.

CTE consists of four large multiprotein complexes, -CI, CII, CIII and CIV-, which have the ability to structurally reorganize in different ways to perform different functions and adapt to environmental conditions, explains Dr. José Antonio Enríquez, head of the Functional Genetics Group of the oxidative phosphorylation system of CNIC and co-author of the research.

The protein SCAF1, which was already discovered in 2013 by the group of Dr. Enríquez, is a key factor in the organization of the ETC. In 2016, the same group described in a study, using mice and zebrafish as models, that this factor is essential for optimizing energy efficiency in high-demand situations.

Complexes I, III and IV of the mitochondrial electron transport chain combine into large structures called supercomplexes. SCAF1 establishes connectivity between mitochondrial transport chain complexes. (Image: CNIC)

The work, led by Dr. Auwerx, from the Federal Polytechnic School of Lausanne (EPFL) in Switzerland, shows that SCAF1 expression in humans is regulated by population genetic variants. The data obtained in humans, explains Dr. Sara Cogliati, “shows that there is a genetic variable SCAF1 that determines higher expression in muscle and heart”.

Therefore, explains Dr. Cogliati, “individuals with this variable have lower body fat mass and better cardiorespiratory capacity during exercise.”

The study also shows that this genetic variable is distributed differently among populations on different continents, “suggesting a possible adaptive role of the organization of the ETC in different environmental situations,” Dr. Enríquez points out.

The study’s findings, the authors say, not only provide new and revealing information about the genetic basis of how these variants affect mitochondrial supercomplex formation in human muscle, but also demonstrate the importance of COX7A2L and SC to cardiometabolic fitness and human health.

“Cardiorespiratory fitness is an important predictor of cardiovascular and metabolic health. Improving cardiorespiratory fitness and exercise capacity is a very promising strategy for reducing cardiovascular and all-cause mortality,” Dr. Cogliati points out.

The researchers conclude that these results define for the first time in humans the fundamental role of the ETC as a key element in the adaptation of metabolism to different energy demands. (Source: CNIC)