A/Prof Michael Lazarou, Lab Head | WEHI Researcher Profile

About

Michael’s work focuses on autophagy and mitochondrial quality control. The lab uses multiple imaging modalities, including AI-directed volumetric electron microscopy, combined with gene editing and biochemistry to understand the intricate mechanisms of mitophagy and mitochondrial quality control.

Parkinson’s disease (PD) is one of the most common of the neurodegenerative disorders, affecting 1-2% of the population worldwide. Evidence suggests mitochondrial dysfunction is a central player in the pathogenesis of PD.
Over the last 10 years Michael’s research has focused on solving the mechanisms of PINK1/Parkin mitophagy resulting in a number of ground-breaking discoveries that have advanced our knowledge of the pathway and have informed new therapeutic approaches.

Education

Joint appointments

Awards

Fellowships

Publications

Selected publications from A/Prof Michael Lazarou

Adriaenssens E, Schaar S, Cook ASI, Stuke JFM, Sawa-Makarska J, Nguyen TN, Ren X, Schuschnig M, Romanov J, Khuu G, Lazarou M, Hummer G, Hurley JH, Martens S. Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery. 2024;5(09-09):10.1101/2024.08.28.609967

Nguyen-Dien GT, Townsend B, Kulkarni PG, Kozul K-L, Ooi SS, Eldershaw DN, Weeratunga S, Liu M, Jones MJ, Millard SS, Ng DC, Pagano M, Bonfim-Melo A, Schneider T, Komander D, Lazarou M, Collins BM, Pagan JK. PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCFFBXL4. EMBO Reports. 2024;25(8):10.1038/s44319-024-00181-y

Tudorica DA, Basak B, Cordova ASP, Khuu G, Rose K, Lazarou M, Holzbaur ELF, Hurley JH. A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy. Journal of Cell Biology. 2024;223(7):10.1083/jcb.202309015

Adriaenssens E, Nguyen TN, Sawa-Makarska J, Khuu G, Schuschnig M, Shoebridge S, Skulsuppaisarn M, Watts EM, Csalyi KD, Padman BS, Lazarou M, Martens S. Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD. Nature Structural & Molecular Biology. 2024;:10.1038/s41594-024-01338-y

Saunders TL, Windley SP, Gervinskas G, Balka KR, Rowe C, Lane R, Tailler M, Nguyen TN, Ramm G, Lazarou M, De Nardo D, Kile BT, McArthur K. Exposure of the inner mitochondrial membrane triggers apoptotic mitophagy. Cell Death & Differentiation. 2024;31(3):10.1038/s41418-024-01260-2

Rao S, Skulsuppaisarn M, Strong LM, Ren X, Lazarou M, Hurley JH, Hummer G. Three-step docking by WIPI2, ATG16L1, and ATG3 delivers LC3 to the phagophore. Science Advances. 2024;10(6):10.1126/sciadv.adj8027

Gan ZY, Callegari S, Nguyen TN, Kirk NS, Leis A, Lazarou M, Dewson G, Komander D. Interaction of PINK1 with nucleotides and kinetin. Science Advances. 2024;10(3):10.1126/sciadv.adj7408

Uoselis L, Nguyen TN, Lazarou M. Mitochondrial degradation: Mitophagy and beyond. Molecular Cell. 2023;83(19):10.1016/j.molcel.2023.08.021

Uoselis L, Lindblom R, Lam WK, Küng CJ, Skulsuppaisarn M, Khuu G, Nguyen TN, Rudler DL, Filipovska A, Schittenhelm RB, Lazarou M. Temporal landscape of mitochondrial proteostasis governed by the UPRmt. Science Advances. 2023;9(38):10.1126/sciadv.adh8228

Nguyen‐Dien GT, Kozul K, Cui Y, Townsend B, Kulkarni PG, Ooi SS, Marzio A, Carrodus N, Zuryn S, Pagano M, Parton RG, Lazarou M, Millard SS, Taylor RW, Collins BM, Jones MJ, Pagan JK. FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. The EMBO Journal. 2023;42(13):10.15252/embj.2022112767