Mitochondria are important organelles that produce about 90% of the ATP metabolized in cells. In addition, they play multiple roles in processes such as ion homeostasis, cell growth, redox state maintenance, cell signaling, and stress response. Therefore, mitochondrial function is critical for the regulation of cell function, as well as being associated with the onset and progression of diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, and metabolic diseases. For example, short transmembrane protein 1 (STMP1), a 47-mer transmembrane micropeptide localized to the mitochondrial inner membrane, is upregulated in various cancer cells and is associated with cancer metastasis and recurrence. It has been reported that overexpression of STMP1 promotes mitochondrial fission and enhances tumor cell migration. Further, knockdown of STMP1 suppresses mitochondrial fission, suggesting it may be a potential target for cancer therapy. For this reason, mitochondria and mitochondrial proteins that control mitochondrial function have attracted great attention as drug targets in recent years, but few drugs or therapies have yet been approved. The main reason for this is considered to be the complexity of mitochondrial biology. Consequently, the achievement of TPD in mitochondria (mitoTPD) is expected to contribute greatly to the elucidation of mitochondrial biology, as well as expanding drug discovery options. Indeed, quite recently, TPD strategies for degrading mitochondrial proteins have begun to be developed. Herein, we describe the design and synthesis of a bifunctional molecule comprising TR79, an activator of the mitochondrial protease complex caseinolytic protease P (ClpP), linked to desthiobiotin, and we show that it can rapidly induce the degradation of monomeric streptavidin (mSA) and an mSA-fused protein of interest overexpressed in mitochondria. As proof of concept, we demonstrate that in cells overexpressing mSA-STMP1 fusion protein, which enhances mitochondrial fission, our degrader restored the mitochondrial morphology by reducing the level of mSA-STMP1, thereby enabling control of mitochondrial morphology. We believe these results advance the prospects for employing mitoTPD as a modality to develop drugs targeting mitochondrial proteins, as well as validating the mSA-based degradation tag platform as a useful tool to study mitochondrial biology.