A limitation of our study is that we targeted artificially expressed mSA and its fusion protein within the mitochondria, but not endogenous mitochondrial proteins. Nevertheless, it is noteworthy that we achieved the degradation of the fusion protein of STMP1, a transmembrane protein localized to the mitochondrial inner membrane, suggesting the applicability of mitoTPD technology not only to the mitochondrial matrix, but also to inner membrane-localized proteins whose ligand binding site is exposed to the matrix. Various PROTACs targeting protein tags such as HaloTag and FKBP12 F36V have been reported and have been employed as rapid knockdown tools for biological research. Our mitochondrial mSA-tag degraders may therefore prove useful as research tools for mitochondrial biology. The use of biotin and its analogs in cells raises concerns about bioorthogonality, given that biotin functions as a coenzyme in cells. Indeed, to our knowledge, there has been no report of utilizing biotin-binding proteins, including mSA, as PROTAC degradation tags. However, in the case of bacteria, it has been reported that the affinity of desthiobiotin for protein biotin ligases is very low or undetectable. This implies that desthiobiotin would be a bioorthogonal molecule in mammals that lack avidin, and based on this, we employed the combination of mSA and desthiobiotin in this study, demonstrating for the first time its value as a cellular degradation tag. Independently of our research, Wang et al. recently reported a TPD technology for mitochondrial proteins. They employed the known compound ONC201 as a ClpP activator and developed a degrader targeting human mitochondrial RNA polymerase (POLRMT), an intramitochondrial protein.