TAT ‐MTS‐MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM‐deficient cells

In this study, we used heterologous MTSs of human, nuclear‐encoded mitochondrial proteins, to target the human MCM protein into the mitochondria. All fusion proteins reached the mitochondria and successfully underwent processing. Treatment of MMA patient fibroblasts with these fusion proteins restored mitochondrial activity such as ATP production, mitochondrial membrane potential and oxygen consumption, indicating the importance of mitochondrial function in this disease. Treatment with the fusion proteins enhanced cell viability and most importantly reduced MMA levels. Treatment also enhanced albumin and urea secretion in a CRISPR/Cas9‐engineered HepG2 MUT (‐/‐) liver cell line. Therefore, we suggest using this TAT‐MTS‐Protein approach for the treatment of MMA.

Source: Journal of Cellular and Molecular Medicine - December 19, 2017 Category: Molecular Biology Authors: Tal Erlich ‐Hadad, Rita Hadad, Anat Feldman, Hagar Greif, Michal Lictenstein, Haya Lorberboum‐Galski Tags: Original Article Source Type: research