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Sanchez 2015 Abstract MiP2015

From Bioblast
Novel complex I assembly factor mutation leads to adult phenotype.


Sanchez LM, Van den Brand M, Nijtmans LG, Rodenburg RJ (2015)

Event: MiP2015

Complex I (CI) deficiency is the most common enzymatic defect of the oxidative phosphorylation system in childhood (OMIM 252010) and can cause a wide range of clinical phenotypes [1]. It is often caused by an impaired assembly, a process which is still poorly understood. The enzyme is composed of 44 different subunits and its biogenesis requires chaperones or assembly factors which years were shown to be vital proteins for the process.

Whole exome screening of CI deficient patients led us to a patient with a mutated TMEM126B, a recently discovered assembly factor of CI [2]. By lentiviral complementation we could establish that this protein is the cause of the severe CI reduction, in activity as well as its total amount, likely leading to the patient phenotype. Moreover, two dimensional blue native electrophoresis demonstrated that the mutation leads to an impairment of CI assembly at a specific stage of the assembly process.

These new data allow us to better interpret CI assembly defects, and also to better correlate clinical data with biochemical data providing us a better rationale for possible therapeutic approaches.

โ€ข O2k-Network Lab: DE Duesseldorf Roden M, NL Nijmegen Rodenburg R

Labels: MiParea: mtDNA;mt-genetics, Patients 

Organism: Human 

Enzyme: Complex I 

Event: A1, Poster  MiP2015 


Nijmegen Centre Mitochondrial Disorders, Dept Pediatrics, Radboud Univ Medical Centre, Nijmegen, The Netherlands. - [email protected]

References and acknowledgements

  1. Kirby DM, Crawford M, Cleary MA, Dahl HH, Dennett X, Thorburn DR. (1999) Respiratory chain complex I deficiency: an under diagnosed energy generation disorder. Neurology 52:1255โ€“64.
  2. Heide H, Bleier L, Steger M, Ackermann J, Drose S, Schwamb B, Zornig M, Reichert AS, Koch I, Wittig I, Brandt U (2012) Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex. Cell Metab 16:538-49.