Mutation in p97 causing IBMPFD might impact interaction with its cofactor UBXD1
 
Lara Sironi¹, Ana Bento², Claudia Bippes², Albert Neutzner², Stephan Frank^1
1Dept. Neuropathology, Basel University Hospital, Basel, Switzerland; ²Department of Biomedicine Basel University Hospital, Basel, Switzerland
 
The AAA-ATPase valosin containing protein p97/VCP is the central component of the retrotranslocation machinery that is necessary for proteasomal degradation of organellar proteins, involved in the removal of misfolded proteins at different locations to prevent protein stress in the cell. A novel heterozygous missense mutation (I206F) in the conserved linker 1 domain of p97/VCP was found in a Swiss family with hereditary inclusion body myopathy and dementia (IBMPFD). By yeast-2-hybrid we found a change in interaction strength between p97 upon mutation with one of its cofactors, UBXD1. This interaction might be important for p97 translocation to mitochondria during mitophagy, as in a IBMPFD patient, these organelles showed inclusion formation. First results show a stronger interaction between two disease-relevant p97 mutants and UBXD1, compared to wildtype p97. Further studies are required to elucidate the consequences of p97 mutations in the context of mitophagy.