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Breakdown of mitochondrial proteostasis activates quality control pathways including the mitochondrial unfolded protein response (UPRmt) and PINK1/Parkin mitophagy. However, beyond the up-regulation of chaperones and proteases, we have a limited understanding of how the UPRmt remodels and restores damaged mitochondrial proteomes. 

The ability to balance conflicting functional demands is critical for ensuring organismal survival. The transcription and repair of the mitochondrial genome requires separate enzymatic activities that can sterically compete, suggesting a life-long trade-off between these two processes.

RNA-binding proteins and mitochondrial ribosomes have been found to be linchpins of mitochondrial gene expression in health and disease. The expanding repertoire of proteins that bind and regulate the mitochondrial transcriptome has necessitated the development of new tools and methods to examine their molecular functions.

Investigators: Professor Aleksandra Filipovska, Dr Stefan Siira Project description  This project will focus on new and cutting-edge development of

Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved.

Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet.

Aleksandra Filipovska BSc PhD Louis Landau Chair in Child Health Research; NHMRC Leadership Fellow; Deputy Director, ARC Centre of Excellence for

Researchers from The Kids Research Institute Australia and The University of Western Australia have developed a new technique to see inside cells with unprecedented detail, revealing a complicated web of interactions that provides new insights into how cells stay healthy.

The generous support of West Australians through Channel 7’s Telethon Trust will help support vital child health research at The Kids Research Institute Australia in 2023.

Two research teams, led by The Kids Research Institute Australia, have been awarded more than $2 million to fund innovative projects.