MiPsummer Programme pdf - Mitochondrial Physiology Society

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Abstract # 17
Mitochondrial complex IV dysfunction in blood cells from ALS patients
Johannes Ehinger MD 1 , Saori Morota PhD 1 , Gesine Paul‐Visse MD 2 , Eskil Elmr MD, PhD 1, 3
1Mitochondrial Pathophysiology Unit, und University, und, Sweden
2Departent of eurology, Skne University Hospital, und University, und, Sweden
3Department of Clinical europhysiology, Skne University Hospital, und University, und, Sweden
Background Mitochondrial dysfunction is implicated in Amyotrophic ateral Sclerosis (AS)
but the eact role of the mitochondria in the pathogenesis is not known. AS is suspected to
be a systemic disease with its primary symptoms from the nervous system and abnormalities
in both CS‐ and muscle mitochondria have been shown in AS patients.
Objectives e hypothesized that mitochondrial dysfunction could be detected in peripheral
blood mononuclear cells (PBMC) and platelets from AS patients.
Methods Blood samples were acuired from 2 patients diagnosed with AS and agematched
controls. hrombocytes and PBMC were isolated and mitochondrial oygen
consumption was measured in intact and permeabilized cells with addition of mitochondrial
substrates, inhibitors and uncouplers. Respiratory values were normalized for cell count,
citrate synthase activity (CS) and mitochondrial DA content respectively.
Results he activity of mitochondrial Comple I (CI) per cell was increased in thrombocytes
from AS patients. hen normalized for CS, Comple IV (CIV) activity was decreased in AS
patients in both cell types and no difference was detected in CI. However, a significant
decrease in CI activity in stage AS patients compared to stage 2 was seen in PBMCs (see
figure) CS per cell was significantly higher in AS patient than control platelets.
Conclusions CIV‐activity per mitochondria is reduced in AS patients compared to control
and there appears to be a compensatory increase in mitochondrial content in cells from AS
patient. he results indicate that mitochondrial dysfunction is more pronounced in late stage
AS disease.
Mitochondrial complex 1 respiration
O 2 comsumption (pmol/s/CS)
8
6
4
2
0
*
2
3
4
ALS Disease Stage