Defects in mitochondrial fat metabolism can also impact how sugars are metabolized in mitochondrial disorders

Lead researcher

Dr Matthew McKenzie

Main finding

Mitochondrial fat metabolism is the primary source of energy once glycogen stores have been depleted during times of fasting or high energy demand. Defects in mitochondrial fat metabolism can result in liver, heart and brain dysfunction, which in some cases is fatal.
We have found that primary defects in mitochondrial fat metabolism can also cause secondary defects in mitochondrial oxidative phosphorylation (OXPHOS), resulting in the disruption of sugar metabolism. Identifying this combined defect has provided new insights into the complex mechanisms which underlie mitochondrial disease pathology.


Centre for Innate Immunity & Infectious Diseases

Research group

Molecular Basis of Mitochondrial Disease


Sze Chern Lim, Makiko Tajika, Masaru Shimura, Kirstyn T. Carey, David A. Stroud, Kei Murayama, Akira Ohtake and Matthew McKenzie

Journal and article title

Most surprising

We found that the loss of a specific protein involved in mitochondrial fat metabolism disrupts both the assembly and stability of the OXPHOS protein complexes. This loss of stability has not been shown before, and suggests that critical interactions between key proteins are required to maintain both fat and sugar metabolism within the mitochondria.

Future implications

Maintaining high glucose levels is used to treat symptoms in some patients with defects in mitochondrial fat metabolism, however this is not always successful. Our findings provide a novel explanation, as the presence of secondary OXPHOS defects in these patients will also disrupt sugar metabolism, rendering glucose treatment ineffective. Our work also highlights the need for new combination therapies that can reverse defects in both fat and sugar metabolism simultaneously.

Disease/health impact

Mitochondrial Disease