Jens Frey Halling – University of Copenhagen

Jens Frey Halling

Role of PGC-1α in exercise training-induced regulation of mitochondrial structure and mitophagy

During my Master's thesis it became increasingly obvious to me that although the field of exercise physiology was started by August Krogh and others more than 100 years ago it still contains many exciting and largely undiscovered areas which motivated me to pursue a career within academic physiology research.

The results obtained during my Master's thesis revealed that in addition to inducing mitochondrial biogenesis, endurance exercise training stimulates recently discovered mitochondrial quality control pathways including mitochondrial fission/fusion and mitophagy in mouse skeletal muscle. Furthermore, the results suggested a role of the known regulator of mitochondrial biogenesis, PGC-1α, in coordinately regulating several mitochondrial quality control pathways.

Receiving the August Krogh Centre scholarship allowed me to continue working on a project related to and directly following my Master's thesis with the aim of investigating the role of PGC-1α in exercise training-induced regulation of mitochondrial network structure. I got the opportunity to learn confocal microscopy imaging techniques to assess mitochondrial network structure in isolated single muscle fibers from leading experts which will undoubtedly be of great importance for the present and future projects.

Although the project described in the application included microscopy analyses on muscle samples from young untrained/trained mice with muscle-specific overexpression of PGC-1α, fascinating results from a concurrent study in our lab suggested that aging is associated with changes in mitochondrial structure with possible detrimental effects on muscle function. Therefore, the mitochondrial microscopy analyses supported by the August Krogh Centre were performed on samples from a study on aged PGC-1α knockout mice and their littermate wild-types with or without lifelong access to running wheels. Briefly, the results obtained in the project indicated that exercise training protects against aging-induced mitochondrial fragmentation in a PGC-1α dependent manner.

Preliminary results were presented at the Cell Symposia - Exercise Metabolism conference in Amsterdam (July 2015) and the final analyses on the possible molecular mechanisms behind our observations are ongoing with the aim of submitting a paper within the coming months. Furthermore, receiving the August Krogh Centre scholarship was likely a contributing factor in receiving funding for a PhD project which I have recently started.