MiPsummer Programme pdf - Mitochondrial Physiology Society

60
Abstract # 30
Characterization of complex III deficiency caused by myxothiazol administration in wild type
mice
Mina Davoudi 1 , Jukka Kallijärvi 2 , Sanna Marjavaara 2 , Eva Hanson, Per Levéen 1,2 , Heike Kotarsky 1 ,
Vineta Fellman 1,2,3
1 Division of Pediatrics, Department of Clinical Sciences, Lund, Lund University, Lund, 22185
Sweden
2 Folkhälsan Research Institute, Helsinki, 00029 Finland
3 Children´s Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, 00029 Finland
A common cause of complex III (CIII) deficiency with liver disorder is mutations in the assembly
factor BCS1L leading to depletion of Rieske iron sulfur protein (RISP) in CIII. We wanted to study
the impact of RISP inhibition on the formation of respiratory chain complexes and supercomplexes.
By administering myxothiazol to inhibit RISP in 5-6 wks old wild type mice (0.56 mg/kg body
mass i.p 1- 5 times) we induced CIII deficiency for liver studies. Control mice were given saline
with DMSO. After 24, 48, 72, and 74 h animals (n=3/group) were sacrificed and liver mitochondria
isolated. CIII-activity was decreased to 50% of control. In the main supercomplexes, myxothiazol
treated mice demonstrated increased amount of both complex III (containing RISP) and complex I.
Free complex I was also increased. We conclude that myxothiazol induced CIII inhibition causes a
compensatory increase of complex I and III content in the supercomplexes.