Mitochondrial DNA

Mitochondria are considered the powerhouse of the cell as they produce the majority of the energy required for cell function. One of the intriguing properties of these specialised organelles is that they possess their own DNA that encodes key elements of the oxidative phosphorylation system.

Defects in mitochondrial DNA have long been associated with human disease such as neurodegeneration. Similarly to nuclear DNA, mitochondrial DNA interacts with various proteins and gets organised into nucleoprotein complexes, or nucleoids. The protein components of the nucleoids serve to protect, segregate and express mitochondrial DNA. They include two elements of the actin cytoskeleton: beta-actin — which is located in the mitochondrial matrix — and non-muscle myosin heavy chain IIA (NM-IIA).

However, our understanding of the function of these DNA transacting proteins is incomplete. More detailed characterisation is, therefore, required to comprehend their implication in mitochondrial DNA metabolism and disease.

The scope of the EU-funded 'Elucidating the roles of proteins of mitochondrial DNA maintenance' (MITOSKELETON) project was to examine the role of mitochondrial DNA interacting proteins in the movement and transmission of mitochondrial DNA. In addition, the performed experiments were designed to identify putative protein partners.

MITOSKELETON results showed that non-muscle myosin heavy chain proteins NM-IIA and NM-IIB have a regulatory role in mitochondrial protein synthesis. In addition, targeting of beta-actin causes nucleoid enlargement, supporting its implication in mitochondrial DNA metabolism.

Collectively, these findings provide fundamental insight into the interaction of proteins with mitochondrial DNA. Given the fact that mitochondrial DNA research is still in its infancy, this study should pave the way towards understanding the association between mitochondrial DNA and disease.