Deficient mitophagy pathways in sickle cell disease.
Suella MartinoJean-Benoit ArletMarie-Hélène OdièvreVincent JullienMartina MorasClaude HattabThibaud LefebvreLaurent GouyaMariano Anibal OstuniSophie D LefevreCaroline Le Van KimPublished in: British journal of haematology (2021)
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.
Keyphrases
- sickle cell disease
- end stage renal disease
- oxidative stress
- ejection fraction
- cell death
- newly diagnosed
- chronic kidney disease
- prognostic factors
- reactive oxygen species
- induced apoptosis
- endoplasmic reticulum
- red blood cell
- heat shock protein
- dna damage
- cell proliferation
- high resolution
- heat stress
- cell cycle arrest
- heat shock
- patient reported