Boston University Medical Campus
Evans Center for Interdisciplinary Biomedical Research

Mitochondria ARC (mtARC): Mitochondrial Dynamics in Health

Please  Note Our Upcoming Events

7/11/12

4:00 pm           Workshop organized by the MitoARC: Approaches to the measurement of autophagy and autophagic flux Presented by Andrew Ferree and Orian Shirihai

INITIATION DATE:

12.01.09

ARC DIRECTORS AND CO-DIRECTORS:

Director, Orian Shirihai; Associate Professor; Medicine/Obesity/BUSM

Co-Dir, Andrea Havasi; Assistant Professor; Medicine/Nephrology/BUSM

OVERVIEW OF GOALS AND MISSION:

The mtARC is comprised of 22 labs with shared interest in the role of mitochondria in pathophysiology. Diverse membership encompasses 11 sections/departments with representation from both the Medical and Charles River Campuses.  In addition, membership includes labs from other universities and from industry. In its first year, the mtARC will collaborate on the study of mitochondrial fusion and fission, collectively termed “Mitochondrial Dynamics”. These processes underlie the maintenance of a healthy mitochondrial population by permitting complementation of underperforming units and removal of dysfunctional units by autophagy. Of particular interest is the role of Mfn2 in the pathophysiology of disease. Mfn2 is essential for mitochondrial fusion and has been associated with CMT2A and more recently with obesity and diabetes.  Members of the mtARC are focused on the role of Mfn2 in cardiovascular disease, metabolic complications, renal disorders, and neurodegeneration and in the mechanisms by which Mfn2 modulates apoptosis and ROS signaling. To address these questions, the mtARC will provide training and tools for investigating mitochondrial bioenergetics, dynamics and ROS in various systems, as well as develop cells lines and animal models of Mfn2 overexpression. Our aim is to accelerate the study of mitochondrial function through education, service, and scientific advancement.

ARC Members:

MAIN ARC PROJECT(S) FOR 2009-2010:

The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission result in deterioration of mitochondrial respiratory function. Moreover, alterations in the balance between fusion and fission activity influence cell proliferation and apoptosis. Recent data indicate that mitochondrial fusion and fission execute their effect on mitochondrial bioenergetics by affecting the ability of mitochondria to deal with ROS; conversely, changes in mitochondrial fission largely impact ROS production by mitochondria.

Of the regulators of mitochondrial dynamics, mitochondrial fusion protein 2 (MFN2) has attracted the attention of multiple labs in the mtARC. Results from a number of labs indicate that alterations in the levels and function of Mfn2 play a role in diabetes and cardiovascular disease.  In beta and endothelial cells, changes in Mfn2 were triggered by nutrient induced oxidative stress, suggesting the possibility that similar mechanisms affect mitochondrial dynamics in different tissues leading to diverse phenotypes.

The goals of the ARC project is to determine the role of mitochondrial dynamics, and in particular Mfn2, in the pathophysiogy of multiple diseases of interest. We rationalized that focusing on one mediator of mitochondrial dynamics, i.e. Mfn2, will allow the group to generate valuable molecular and genetic tools that can be used for the study of several disease models and that any mechanistic information revealed in one disease model  could be then tested in the other models, amplifying the impact of each discovery.

ARC AS A RESOURCE:

A group of labs at the mtARC will form the mtARC-Core that will provide tools and guidance to facilitate the use of technologies to be applied in all systems below. The mtARC-Core includes A. Bioenergetics (Drs. Shirihai, Ferrick), B. Imaging (Dr. Molina), C. ROS (Drs. Doctrow, Cohen, Goldstein), D. Molecular , including Mfn2 expression viruses and transgenic mice. and  E. human Genetics (Dr.  Schwartz and Dr. Levy).

Pictures, Images, Figures: