Granata 2022 Abstract Bioblast

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Granata Cesare (2022) Exercise training-induced enhancement of electron flow to the OXPHOS system is more important than increasing the OXPHOS machinery content to improve ATP generation in human skeletal muscle. Bioblast 2022: BEC Inaugural Conference.

Link: Bioblast 2022: BEC Inaugural Conference

Granata Cesare (2022)

Event: Bioblast 2022

Mitochondrial health is implicated in multiple diseases and ageing, and is therefore an important determinant of an individual’s quality of life [1]. Exercise training is an accessible and inexpensive therapeutic intervention that is extensively used to prevent, treat, and manage several lifestyle diseases [2], by enhancing mitochondrial biogenesis and improving mitochondrial bioenergetics. However, the intricacy of exercise training-induced mitochondrial adaptations remains, for the most part, unknown.

By utilizing a multi-omics approach integrated with classic biological mitochondrial techniques we performed an in-depth investigation of the effects of three different and sequential volumes of high-intensity interval training on the mitochondrial transcriptome, proteome, and lipidome in human skeletal muscle (n=10) [3].

We first confirmed that changes in mitochondrial respiration, content, and enzymatic activity, as well as supercomplex formation and the content of selected subunits of the OXPHOS system mirrored, for the most part, the changes in training volume, and that these changes were driven by the overall increase in mitochondrial content, as previously demonstrated [4]. Subsequently, by combining the power of 3 omics techniques with biochemical and in silico normalization, we removed the bias arising from the training-induced increase in mitochondrial content to unearth an intricate and previously undemonstrated network of differentially prioritized mitochondrial adaptations. We show that changes in hundreds of transcripts, proteins, and lipids are not stoichiometrically linked to the overall increase in mitochondrial content. Our findings indicate that enhancing electron flow to the OXPHOS system is more important to improve ATP generation than increasing the abundance of the OXPHOS machinery, and do not support the hypothesis that training-induced supercomplex reorganization enhances mitochondrial bioenergetics [3].

Our study provides an analytical approach allowing unbiased and in-depth investigation of training-induced mitochondrial adaptations that challenges our current understanding and calls for careful reinterpretation of previous findings.

Keywords: OXPHOS, Mitochondria, Exercise training, Proteomics, Lipidomics Bioblast editor: Plangger M O2k-Network Lab: DE Duesseldorf Roden M


Affiliations

Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine Univ, 40225 Düsseldorf, Germany
German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany. –cesare.granata@ddz.de

Figures

Figure 1: Overview of training-induced changes in mitochondrial protein functional classes related to ATP generation. Row clustering determined by unsupervised hierarchical cluster analysis. FAO fatty acid β-oxidation, TCA tricarboxylic acid cycle, OXPHOS oxidative phosphorylation.

References

  1. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148:1145-59. doi: 10.1016/j.cell.2012.02.035
  2. Pedersen BK, Saltin B (2015) Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25:1-72.
  3. Granata C, Caruana NJ, Botella J, Jamnick NA, Huynh K, Kuang J, Janssen HA, Reljic B, Mellett NA, Laskowski A, Stait TL, Frazier AE, Coughlan MT, Meikle PJ, Thorburn DR, Stroud DA, Bishop DJ (2021) High-intensity training induces non-stoichiometric changes in the mitochondrial proteome of human skeletal muscle without reorganisation of respiratory chain content. Nature Commun 12:7056.
  4. Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ (2016) Mitochondrial adaptations to high-volume exercise training are rapidly reversed after a reduction in training volume in human skeletal muscle. FASEB J 30:3413-23.

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Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Human  Tissue;cell: Skeletal muscle 



HRR: Oxygraph-2k