mitochondrial dysfunction
Posted: Tue Aug 22, 2006 7:45 am
Mitochondrial dysfunction seems to be getting quite a bit of research attention these days, lets hope all the study leads to effective therapies.
Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis.
J Biol Chem. 2006 Aug 18;
Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J.
Ophthalmology, University of Florida, Gainesville, FL 32605.
The mechanisms of axonal and neuronal degeneration causing visual and neurologic disability in multiple sclerosis are poorly understood. Here we explore the contribution of mitochondria to neurodegeneration in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis.
Oxidative injury to the murine mitochondrion preceded the infiltration of inflammatory cells, classically heralded as the mediators of demyelination and axonal injury by transection. Nitration of mitochondrial proteins affected key subunits of complexes I and IV of the respiratory chain and a chaperone critical to the stabilization and translocation of proteins into the organelle. Oxidative products were associated with loss of mitochondrial membrane potential and apoptotic cell death. Reductions in ATP synthesis were severe and even greater than those associated with disorders caused by mutated mitochondrial DNA. Mitochondrial vacuolization, swelling and dissolution of cristae occurred in axons as early as 3 days after sensitization for EAE.
Our findings implicate mitochondrial dysfunction induced by protein inactivation and mediated by oxidative stress initiates a cascade of molecular events leading to apoptosis and neurodegeneration in EAE that is not mediated by inflammatory cells.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis.
J Biol Chem. 2006 Aug 18;
Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J.
Ophthalmology, University of Florida, Gainesville, FL 32605.
The mechanisms of axonal and neuronal degeneration causing visual and neurologic disability in multiple sclerosis are poorly understood. Here we explore the contribution of mitochondria to neurodegeneration in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis.
Oxidative injury to the murine mitochondrion preceded the infiltration of inflammatory cells, classically heralded as the mediators of demyelination and axonal injury by transection. Nitration of mitochondrial proteins affected key subunits of complexes I and IV of the respiratory chain and a chaperone critical to the stabilization and translocation of proteins into the organelle. Oxidative products were associated with loss of mitochondrial membrane potential and apoptotic cell death. Reductions in ATP synthesis were severe and even greater than those associated with disorders caused by mutated mitochondrial DNA. Mitochondrial vacuolization, swelling and dissolution of cristae occurred in axons as early as 3 days after sensitization for EAE.
Our findings implicate mitochondrial dysfunction induced by protein inactivation and mediated by oxidative stress initiates a cascade of molecular events leading to apoptosis and neurodegeneration in EAE that is not mediated by inflammatory cells.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum