In our latest review, Luke Formosa, Marris Dibley, David Stroud and Mike Ryan outline the current understanding of mitochondrial complex I assembly, focussing on the role and importance of complex I assembly factors during this process.
Mitochondrial complex I is the primary entry point for electrons into the electron transport chain, required for the bulk of cellular ATP production via oxidative phosphorylation. Complex I consists of 45 subunits, which are encoded by both nuclear and mitochondrial DNA. Currently, at least 15 assembly factors are known to be required for the complete maturation of complex I. Mutations in the genes encoding subunits and assembly factors leads to complex I deficiency, which can manifest as mitochondrial disease. The current model of complex I assembly suggests that the enzyme is built by the association of a set of smaller intermediate modules containing specific conserved core subunits and additional accessory subunits. Each module must converge in a spatially and temporally orchestrated fashion to allow assembly of the mature holoenzyme to occur. This review outlines the current understanding of complex I biogenesis, with an emphasis on the assembly factors that facilitate the building of this architectural giant.
Please click here to see the publication.
Dr David Stroud, a NHMRC Doherty Fellow from our lab, co-lead a study with collaborators from the Murdoch Children’s Research Institute, investigating the genetic underpinnings and proteomic changes of patients with Leigh Syndrome.
Their research revealed that mutations in the MRPS34 gene, a component of the mitoribosome, leading to severe effects on the protein synthesis of mitochondrial encoded proteins required for mitochondrial respiration and energy production.
The publication in the American Journal of Human Genetics can be found here.
With some delay (due to the navigation capabilities of one senior PhD student), the Ryan lab members started their annual walk in the late morning from the Cooks Mill Ground up to the Razorback Tail.
After a steep and demanding walk up to the sattle of the mountain ranges, we could enjoy a lunch break with a fantastic view over the Cathedral Ranges.
After lunch, we continued climbing on the back of the Razorback, heading towards the Sugarloaf Peak. Reaching the peak, we turned around and could enjoy a fantastic sunset illuminating the mountain ranges in warm light.
A brief Schnitzel and Parma stop was the adequate pit stop for all of us before we got back into the cars and headed home.
Two new lab members have joined us for their Honours year. Rufus will be working on how to treat mitochondrial dysfunction with pharmaceuticals, while Dylan will be investigating the assembly of complex I.
Good luck to both of you and nice having you around!
A recent publication from the Ryan Lab has revealed that the complex I subunit exists in two isoforms. Published in FEBS Letters in December of 2016, the paper identifies a second long isoform of the peripheral N-module subunit NDUFV3 which exhibits tissue specific expression patterns.
A novel isoform of the human mitochondrial complex I subunit NDUFV3. Marris G. Dibley, Michael T. Ryan, David A. Stroud, FEBS Lett. 2016 Dec 17. doi: 10.1002/1873-3468.12527 Pubmed
Luke Formosa and Mike Ryan preview new research into the structural mechanism of Mitofusin 1 and implications for mitochondrial outer membrane fusion published in The Journal of Cell Biology.
Mitochondrial fusion: Reaching the end of mitofusin's tether. Luke E. Formosa, Michael T. Ryan. J. Cell Biol. 2016 Nov 23. pii: jcb.201611048. PubMed
This Sunday, the Ryan Lab (aka "MonashMitoLab") participated in the 2016 edition of the Bloody Long Walk in Melbourne to raise awareness for mitochondrial diseases.
Taking place with typical Melbourne weather, our long journey started at Yarra Bend Park and took us along the Yarra River through the beautiful Melbourne suburbs and ending at St Kilda Beach.
Despite heavy rain, mud and flooded footpaths, the lab team was excited to go through some pain for the good cause.
After some grueling 35k, which pushed everyone to their limits, we finished in less than 6h and under a blue sky and sunshine in St Kilda.