August Krogh seminar ft. Mike Murphy

Danish Diabetes Academy is co-financing the August Krogh Seminar on 28 April 2017 in Copenhagen entitled "Mitochondrial ROS production in health and disease" by Dr. Mike Murphy from University of Cambridge. All interested researchers are invited on behalf of the August Krogh Club steering committee.

TIME AND PLACE

28 April 2016, 14:00-15:30

Auditorium 1, August Krogh Building
Universitetsparken 13, DK-2100 Copenhagen

PROGRAMME

REGISTRATION

Participation is free, but please register here.
PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar.

MITOCHONDRIAL ROS PRODUCTION IN HEALTH AND DISEASE

v/ Dr. Mike Murphy, MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

ABSTRACT

Mitochondrial oxidative damage has long been known to contribute to damage in conditions such as ischaemia-reperfusion (IR) injury in heart attack. More recently they have also been implicated in redox signalling. Over the past years we have developed a series of mitochondria-targeted compounds designed to ameliorate or determine how this damage occurs. I will outline some of this work, from MitoQ to the mitochondria-targeted S-nitrosating agent, called MitoSNO, that we showed was effective in preventing ROS formation in IR injury with therapeutic implications.

In addition, the protection by this compound suggested that ROS production in IR injury was mainly coming from complex I. This led us to investigate the mechanism of the ROS production and using a metabolomic approach we found that the ROS production in IR injury came from the accumulation of  succinate during ischaemia that then drove mitochondrial ROS production by reverse electron transport at complex I during reperfusion.

This surprising mechanism led up to develop further new therapeutic approaches to impact on the damage that mitochondrial ROS do in pathology and also to explore how mitochondrial ROS can act as redox signals. I will discuss how these unexpected mechanisms may lead to redox signals from mitochondria in conditions such as cancer and inflammation.

RESEARCH BACKGROUND

Dr. Mike Murphy received his BA in chemistry at Trinity College, Dublin in 1984 and his PhD in Biochemistry at Cambridge University in 1987. 

After stints in the USA, Zimbabwe, and Ireland he took up a faculty position in the Biochemistry Department at the University of Otago, Dunedin, New Zealand in 1992. In 2001 he moved to the MRC Mitochondrial Biology Unit in Cambridge, UK (then called the MRC Dunn Human Nutrition Unit) where he is a group leader.

Murphy’s research focuses on the roles of reactive oxygen species in mitochondrial function and pathology. In particular he has pioneered the targeting of bioactive and probe molecules to mitochondria in vivo. This general methodology is now widely used. Prominent mitochondria-targeted compounds are antioxidants, such as MitoQ, which protects against oxidative damage in ischaemia-reperfusion injury.

Murphy developed MitoQ as an oral drug which has been used in two Phase II trials so far. This work established mitochondria as a relevant drug target and opened up the field of mitochondrial pharmacology. The Murphy group has gone on to create MitoSNO, a mitochondria-targeted nitric oxide donor which is now being developed as a potential therapy for cardiac ischaemia-reperfusion injury, and MitoG to treat diabetes. Recently his work has extended to determining the mechanism by which mitochondria produce free radicals during ischaemia-reperfusion injury in heart attack and stroke.

Murphy is a Wellcome Trust Investigator, honorary research Professor at the University of Otago, New Zealand, a recipient of the Keilin Medal from the Biochemical Society and is an honorary Fellow of the Royal Society of New Zealand.  He has published more than 270 papers and has a h-index of 87.

FURTHER INFORMATION

For further information about the seminar

• Go to: akc.ku.dk/calendar/2017/mike-murphy_seminar
• Contact Christian Frøsig: CFrosig@nexs.ku.dk, mobile +45 2875 1617