Mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-α protein (PMPCA) cause a severe mitochondrial disease

Mugdha Joshi, Irina Anselm, Jiahai Shi, Tejus A. Bale, Meghan Towne, Klaus Schmitz-Abe, Laura Crowley, Felix C. Giani, Shideh Kazerounian, Kyriacos Markianos, Hart G. Lidov, Rebecca Folkerth, Vijay G. Sankaran, and Pankaj B. Agrawal. Cold Spring Harb Mol Case Stud. 2016 May; 2(3): a000786. doi:10.1101/mcs.a000786


This study describes a severe mitochondrial disease due to PMPCA mutations in a large family, which we show is associated with altered levels of mature frataxin. Whereas a recent study described cerebellar ataxia as a presentation of PMPCA mutations, the phenotype in our family is more severe and typical of a mitochondrial disease. The observed phenotype may be related to impaired PMPCA function due to a reduction in its level and the resultant abnormal processing of frataxin and other mitochondrial proteins.

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