Professor Phillip Nagley

BSc (Hons), MSc (University of Sydney), PhD, DSc (Monash University)

General Profile:

• I am a Professor of Biochemistry, with enthusiasm for all aspects of Biochemistry and Molecular Biology.
• My particular research interests encompass:
  • mitochondria, oxidative stress and apoptosis
  • the molecular basis of energy production in cells, specifically the molecular biology of the yeast mitochondrial ATP synthase complex.
• I am active in teaching in Science, Biomedical Science and Medicine courses at Monash University.
• I was editor (1998 - 2003) of the Australian Biochemist, the national scientific and news magazine of the Australian Society for Biochemistry and Molecular Biology. I was President-elect of ASBMB (2004). I am now President of ASBMB (2005-2006).
• I was awarded the Lemberg Medal of the Australian Society for Biochemistry and Molecular Biology in 2001.

Current Research Interests:

• Mitochondria and oxidative stress in neuronal injury and cell death
• Significance of mitochondria in survival and death of cancer cells
• The process of release of apoptotic signalling proteins from mitochondria
• Understanding host-pathogen interactions in bacterial infection of mammalian cells
• The structure and function of a molecular machine: yeast mitochondrial ATP synthase - (PDF document: Please refer to page 7)

MAMMALIAN MITOCHONDRIA GROUP - 2005

Back Row Standing (Left to Right): Gavin Higgins, Susan Ekkel, Tania Hansen, Luke Cossins, Phillip Nagley, Jennifer Newman, Danielle Smith, Assunta Pelosi, Maria Lim, Giacinto Gaetano
Front Row (Left to Right): Lesley Cheng, Elaine Pearson, Wun Keat Ding, Heling Ng, Kai Ying Soo

Career Synopsis and Research Profile

Professor Phillip Nagley graduated from the University of Sydney in 1967, where he was awarded the University Medal in Biochemistry. He completed his MSc at the same University before moving to Melbourne to undertake his PhD in the Department of Biochemistry at Monash University. His research work at Sydney encompassed studies of mammalian ribosomes and endoplasmic reticulum, then work on bacterial DNA replication. He integrated these two different experiences to embark on his PhD studies on the formation of mitochondria in yeast cells.

Phillip Nagley's PhD studies, completed in 1972, focussed on a molecular genetic and biochemical study of mitochondrial biogenesis. One highlight of this early work was the discovery he made of yeast cells that lack mitochondrial DNA (mtDNA) completely. These cells were termed rho0 by Nagley and Linnane (1972), a term which is current use today for similar cells that can be isolated from mammalian sources and which are extremely useful in many aspects of research on the role of mitochondria in cellular life and death.

Phillip Nagley has continued his research in the Department of Biochemistry (now Biochemistry and Molecular Biology) at Monash University since 1972, with two periods of sabbatical leave at the University of Paris, France, and Stanford University, California, USA. He has also held Exchange Fellowships for collaboration with scientists in Japan (University of Nagoya, University of Tokushima) and Taiwan (National Yang-Ming University).

He has researched extensively into the formation of mitochondria in yeast, covering many aspects of cell and molecular biology. He was awarded his DSc degree in 1986 for his collected publications to that time, in a thesis entitled The Molecular Biology of Mitochondria. He was awarded a Personal Chair in Biochemistry in 1990. He has published more than 180 publications in international journals and books.

Most of Professor Nagley's research up to 1990 was on the yeast system. This work continues, with a focus on the mitochondrial ATP synthase, but was extended during the 1990s to include work on human ageing. Most recently his work includes detailed studies on the role of mitochondria in cell death. Highlights of his publications since 1998 include the following (total 40 papers over that period):

V.W.S. Liu, C. Zhang and P. Nagley, "Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing." Nucleic Acids Research, 26, 1268-1275 (1998)

P. Nagley and Y.H. Wei, "Aging and mammalian mitochondrial genetics". Trends in Genetics, 14, 513-517 (1998)

T. Minamikawa, D.A. Williams, D.N. Bowser and P. Nagley. "Mitochondrial permeability transition and swelling can occur reversibly without inducing cell death in intact human cells". Experimental Cell Research, 246, 26-37 (1999)

M. Bateson, R.J. Devenish, P. Nagley and M. Prescott, "Single copies of subunits d, OSCP and b are present in the S. cerevisiae mitochondrial ATP synthase". Journal of Biological Chemistry, 274, 7462-7466 (1999)

X. Roucou, I.M. Artika, R.J. Devenish and P. Nagley, "Bioenergetic and structural consequences of allotopic expression of subunit 8 of yeast mitochondrial ATP synthase: The hydrophobic character of residues 23 and 24 is essential for maximal activity and structural stability of the enzyme complex". European Journal of Biochemistry 261, 444-451 (1999)

T. Minamikawa, A. Sriratana, D.A. Williams, D.N. Bowser, J.S. Hill and P. Nagley, "Chloromethyl-X-Rosamine (MitoTracker Red) photosensitises mitochondria and induces apoptosis in intact human cells". Journal of Cell Science, 112, 2419-2430 (1999)

R.J. Devenish, M. Prescott, X. Roucou and P. Nagley, "Insights into ATP synthase assembly and function through the molecular genetic manipulation of subunits of the yeast mitochondrial enzyme complex". Biochimica et Biophysica Acta, 1458, 428-442 (2000)

X. Roucou, M. Prescott, R.J. Devenish and P. Nagley, "A cytochrome c-GFP fusion is not released from mitochondria into the cytoplasm upon expression of bax in yeast cells." Federation of European Biochemical Societies, Letters, 471, 235-239 (2000)

A.N. Stephens, X. Roucou, I.M. Artika, R.J. Devenish and P. Nagley, "Topology and proximity relationships of yeast mitochondrial ATP synthase subunit 8 determined by unique introduced cysteine residues." European Journal of Biochemistry, 267, 6443-6451 (2000)

P. Nagley, C. Zhang, M.L.R. Lim, M. Merhi, B.E. Needham and Z. Khalil, "Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve function". Neurobiology of Aging, 22, 635-643 (2001)

M.L.R. Lim, T. Minamikawa and P. Nagley, "The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells." FEBS Letters, 503, 69-74 (2001)

M.L.R. Lim, M.G. Lum, T.M. Hansen, X. Roucou and P. Nagley, "On the release of cytochrome c from mitochondria during cell death signaling". Journal of Biomedical Science, 9, 488-506 (2002)

M.G. Lum, T. Minamikawa and P. Nagley. "Microscopic photosensitization: a new tool to investigate the role of mitochondria in cell death". TheScientificWorldJOURNAL, 2, 1198-1208 (2002)

M. Prescott, S. Nowakowski, P. Gavin, P. Nagley, J.C. Whisstock and R.J. Devenish. "Subunit g-GFP fusions are functionally incorporated into mitochondrial F1FO ATP synthase arguing against a rigid cap structure at the top of F1". Journal of Biological Chemistry, 278, 251-256 (2003)

M.G. Lum and P. Nagley, "Two phases of signalling between mitochondria during apoptosis leading to early depolarisation and delayed cytochrome c release". Journal of Cell Science, 116, 1437-1447 (2003)

A.N. Stephens, M.A. Khan, X. Roucou, P. Nagley and. R.J. Devenish, "The molecular neighborhood of subunit 8 of yeast mitochondrial F1FO-ATP synthase probed by cysteine scanning mutagenesis and chemical modification." Journal of Biological Chemistry, 278, 17867-17875 (2003)

F. Miller, F.L. Rosenfeldt, C. Zhang, A.W. Linnane and P. Nagley, "Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age." Nucleic Acids Research, 31, e61 (2003)

T.M. Hansen and P. Nagley, "AIF: A multifunctional cog in the death machine". Science's Signal Transduction Knowledge Environment, 2003, pe31 (2003)

A.N. Stephens, P. Nagley and R.J. Devenish, “Each yeast mitochondrial F 0F 1-ATP synthase complex contains one copy of subunit 8”. Biochimicaet Biophysica Acta (Bioenergetics) 1607, 181-189 (2003)

F. Rosenfeldt, F. Miller, P. Nagley, A. Hadj, S. Marasco, D. Quick, F. Sheeran, M. Wowk, and S. Pepe. “Response of the senescent heart to stress. Clinical therapeutic strategies and quest for mitochondrial predictors of biological age”. Annals of the New York Academy of Sciences , 1019, 78-84 (2004)

F. Rosenfeldt, S. Marasco, W. Lyon, M. Wowk, F. Sheeran, M. Bailey, D. Esmore, B. Davis, A. Pick, M. Rabinov, J. Smith, P. Nagley and S. Pepe. “Coenzyme Q 10 therapy before cardiac surgery improves mitochondrial and myocardial contractile function”. Journal of Thoracic and Cardiovascular Surgery, 129, 25-32 (2005)