Fernyhough 2010 Expert Rev Endocrinol Metab
|Fernyhough P, Roy Chowdhury SK, Schmidt RE (2010) Mitochondrial stress and the pathogenesis of diabetic neuropathy. Expert Rev Endocrinol Metab 5:39-49.|
Abstract: Diabetic neuropathy is a major complication of diabetes that affects the sensory and autonomic nervous systems and leads to significant morbidity and impact on quality of life of patients. Mitochondrial stress has been proposed as a major mediator of neurodegeneration in diabetes. This review briefly summarizes the nature of sensory and autonomic nerve dysfunction and presents these findings in the context of diabetes-induced nerve degeneration mediated by alterations in mitochondrial ultrastructure, physiology and trafficking. Diabetes-induced dysfunction in calcium homeostasis is discussed at length and causative associations with sub-optimal mitochondrial physiology are developed. It is clear that across a range of complications of diabetes that mitochondrial physiology is impaired, in general a reduction in electron transport chain capability is apparent. This abnormal activity may predispose mitochondria to generate elevated reactive oxygen species (ROS), although experimental proof remains lacking, but more importantly will deleteriously alter the bioenergetic status of neurons. It is proposed that the next five years of research should focus on identifying changes in mitochondrial phenotype and associated cellular impact, identifying sources of ROS in neurons and analyzing mitochondrial trafficking under diabetic conditions.
• Keywords: Calcium, Dorsal root ganglia, Electron transport chain, Mitochondrial trafficking, Reactive oxygen species, Respiration, Sensory polyneuropathy, Sympathetic neuropathy • Bioblast editor: Plangger M • O2k-Network Lab: CA Winnipeg Fernyhough P, CA Winnipeg Banerji V
Labels: MiParea: Respiration Pathology: Diabetes
Organism: Rat Tissue;cell: Nervous system Preparation: Isolated mitochondria Enzyme: Complex I, Complex IV;cytochrome c oxidase
Coupling state: OXPHOS, ET Pathway: N, CIV HRR: Oxygraph-2k