Deficient mitophagy pathways in sickle cell disease.
Sickle cell disease (SCD) is characterised by chronic haemolysis and oxidative stress. Herein, we investigated 30 SCD patients and found 40% with elevated mitochondria levels (SS-mito+ ) in their mature red blood cells, while 60% exhibit similar mitochondria levels compared to the AA group (SS-mito- ). The SS-mito+ patients are characterised by higher reticulocytosis and total bilirubin levels, lower foetal haemoglobin, and non-functional mitochondria. Interestingly, we demonstrated decreased levels of mitophagy inducers, PINK1 and NIX, and higher levels of HSP90 chaperone in their red cells. Our results highlighted for the first time an abnormal retention of mitochondria in SCD linked with mitophagy-related proteins.
['Martino|Suella|S|', 'Arlet|Jean-Benoit|JB|', 'Odièvre|Marie-Hélène|MH|', 'Jullien|Vincent|V|', 'Moras|Martina|M|', 'Hattab|Claude|C|', 'Lefebvre|Thibaud|T|', 'Gouya|Laurent|L|', 'Ostuni|Mariano A|MA|0000-0001-6769-3786', 'Lefevre|Sophie D|SD|0000-0002-7504-1881', 'Le Van Kim|Caroline|C|0000-0002-3251-1310']
D000328:Adult D000755:Anemia, Sickle Cell D001663:Bilirubin D004912:Erythrocytes D005260:Female D018841:HSP90 Heat-Shock Proteins D006801:Humans D008297:Male D008565:Membrane Proteins D008928:Mitochondria D063306:Mitophagy D011494:Protein Kinases D011518:Proto-Oncogene Proteins D045262:Reticulocytosis D025521:Tumor Suppressor Proteins
mitophagy sickle cell disease mitochondria PINK1/NIX