A17 Targeting mitophagy in huntington’s disease patients’ fibroblasts

Huntington’s disease (HD) belongs to a group of neurodegenerative diseases characterized by features, such as the accumulation of aggregates of misfolded proteins and progressive loss of neurons. Former studies have shown that it is detrimental to maintain a healthy turnover of mitochondrial pool in order to preserve neuronal health. Thereby, quality control mechanisms, such as mitophagy, have arisen attention. However, it was implied that mutant huntingtin protein (mHTT) affects mitophagy in HD at several stages, thereby disabling impaired mitochondria to be engulfed by autophagosomes. Recently, we described mitochondrial impairments in fibroblasts from HD patients. We thereby aim to induce mitophagy via a small-molecule compound, MIND4-17, yet undescribed in this context. Our intention is to study its effect on the selected adaptor proteins and overall mitophagy in human HD fibroblasts, using immunoelectrophoretic methods, electron and fluorescent microscopy, and bioenergetic functional methods. Pilot analyses showed increased expression of certain autophagy markers (LC3-B, SQSTM1/p62), and showed mitochondrial clustering, which is typical for the process of mitophagy. This implies changes in the turnover of mitochondria and might portray MIND4-17 as a feasible tool for therapeutic purposes. Supported AZV-MZCR NU20-04-00136, MZE- QK1910264 and SVV260367 (CU)