We next focused on STMP1, a mitochondrial short peptide enhancing mitochondrial fission, as a target protein to investigate whether mitochondrial morphology could be controlled. Since a ligand and ligand binding site of STMP1 were not available, we utilized mSA as a degradation tag and examined the degradation of mSA-STMP1 fusion protein. Although STMP1 is a trans-inner membrane peptide, we anticipated that mSA fused to the matrix-oriented N-terminus of STMP1 would be exposed to the matrix and would be targetable to our mitoTPD. First, we confirmed that cox8-His6-mSA-STMP1-FLAG (hereafter mSA-STMP1) is expressed in mitochondria (Figure ) and that treatment with compound 1 decreased mSA-STMP1 in a dose-dependent manner (Figure ). Next, we evaluated changes in mitochondrial morphology caused by the expression of mSA-STMP1 and treatment with 1, using fluorescence-microscopic images and an ImageJ/Fiji macro tool, Mitochondria Analyzer. Analysis of the number of mitochondrial branches, branch length, number of branch junctions, and form factor, which indicates mitochondrial shape, showed that expression of mSA-STMP1 leads to mitochondrial fission, resulting in a smaller, less branched structure, in accordance with previous work. Treatment of HeLa cells expressing mSA-STMP1 with 1 successfully restored the changes in mitochondrial morphology, as judged according to all the evaluated factors (Figure ). These results suggest that mitoTPD is able to control mitochondrial morphology. showed that the longer the linker length, the more effectively these compounds induce mSA degradation (Figure ). In particular, 10 μM 3 reduced the mSA level to approx. 20%, suggesting that the longer linker improves not only the half-maximal degradation concentration (DC50), but also the maximum degradation efficacy (Dmax).