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

Publications

Selected publications from Prof Michael Lazarou

Wang Y, Jefferson M, Ramos M, Whelband M, Kreuzer K, Khuu G, Lazarou M, Mccoll J, Lazenby J, Whitchurch CB, Verkade P, Mayer U, Wileman T. The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance. Autophagy Reports. 2025;4(1):10.1080/27694127.2025.2476218

Yamashita S-I, Arai R, Hada H, Padman BS, Lazarou M, Chan DC, Kanki T, Waguri S. The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria. Journal of Cell Biology. 2025;224(7):10.1083/jcb.202408166

Küng C, Lazarou M, Nguyen TN. Advances in mitophagy initiation mechanisms. Current Opinion in Cell Biology. 2025;94:10.1016/j.ceb.2025.102493

Chen M, Nguyen TN, Ren X, Khuu G, Cook ASI, Zhao Y, Yildiz A, Lazarou M, Hurley JH. Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex. Nature Structural & Molecular Biology. 2025;:10.1038/s41594-025-01557-x

Cook ASI, Chen M, Nguyen TN, Cabezudo AC, Khuu G, Rao S, Garcia SN, Yang M, Iavarone AT, Ren X, Lazarou M, Hummer G, Hurley JH. Structural pathway for PI3-kinase regulation by VPS15 in autophagy. Science. 2025;388(6743):10.1126/science.adl3787

Lei Y, Uoselis L, Dialynaki D, Yang Y, Lazarou M, Klionsky DJ. Cancer-associated mutations in autophagy-related proteins analyzed in yeast and human cells. Autophagy. 2025;ahead-of-print(ahead-of-print):10.1080/15548627.2025.2471142

Schmuckli-Maurer J, Bindschedler AF, Wacker R, Würgler OM, Rehmann R, Lehmberg T, Murphy LO, Nguyen TN, Lazarou M, Monfregola J, Ballabio A, Heussler VT. Plasmodium berghei liver stage parasites exploit host GABARAP proteins for TFEB activation. Communications Biology. 2024;7(1):10.1038/s42003-024-07242-x

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;31(11):10.1038/s41594-024-01338-y

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