Mitochondrial perturbance and execution of apoptosis in platelet mitochondria of patients with amyotrophic lateral sclerosis.
Role of platelets have been evinced as a systemic tool in a variety of neurological disorders. Oxidative phosphorylation contributes approximately 80% of total adenosine-tri-phosphate (ATP) production in resting platelets suggesting potential dependence of platelets on modest mitochondrial functioning. Since mitochondria play a pivotal role in regulating metabolic and apoptotic pathways in various neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), we assessed mitochondrial membrane potential (MMP) associated alterations and apoptotic status of platelet mitochondria in ALS patients using case-control approach. Confocal microscopy reflected heterogeneous distribution of JC-1 aggregates and monomers indicating altered MMP in ALS platelets. Our flow cytometry results confirmed greater percentage of mitochondrial depolarization in ALS platelets. Greater exposure of phosphatidyl serine (PS) residue vindicated by annexin V binding and lesser accumulation of mitotracker red in mitochondrial matrix demonstrated initiation of apoptosis in ALS platelets. Our findings corroborate mitochondrial abnormalities such as perturbance of MMP, mitochondrial depolarization, and apoptosis in ALS platelet mitochondria. In conclusion, our study further evinces the involvement of mitochondrial dysfunction in the pathogenesis of ALS and suggests implication of cell death in peripheral tissues apart from motor neurons in ALS.
Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India.
Mohita
M
Shrivastava
S
S
Vivekanandhan
Uttam
U
Pati
Madhuri
M
Behari
Taposh K
TK
Das
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000473:pathology; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001562:Benzimidazoles / Q000032:analysis; D001792:Blood Platelets / Q000473:pathology* / Q000648:ultrastructure; D002232:Carbocyanines / Q000032:analysis; D016022:Case-Control Studies; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D010085:Oxidative Phosphorylation; D010718:Phosphatidylserines / Q000378:metabolism
D017304:Annexin A5; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D008563:Membrane Lipids; D010718:Phosphatidylserines; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine