PINK1 is a key protein involved in the regulation of mitochondrial quality control and the prevention of Parkinson's disease (PD). Loss-of-function mutations in PINK1 are a common cause of early-onset PD. PINK1 is stabilized at the Translocase of Outer Membrane (TOM) complex of damaged mitochondria, which is essential for its activation. This study reports that co-expression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. The study systematically assessed the role of each TOM subunit in PINK1 activation and demonstrated that TOM20 and TOM70 are required for optimal PINK1 activation. The study also showed that TOM40 and its associated subunits TOM7 and TOM22 are essential for PINK1 activation. Structural modeling and mutagenesis studies revealed that the N-terminal and C-terminal extensions (NTE and CTE) of PINK1 interact with TOM20 and TOM70. These interactions are critical for PINK1 stabilization and activation at the TOM complex. The study also showed that TOM70 is required for optimal PINK1 stabilization and activation at the TOM complex. The findings suggest that PINK1 activation at the TOM complex is mediated by interactions with TOM20 and TOM70. These findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD. The study also showed that PINK1 activation is essential for the elimination of damaged mitochondria through mitophagy. The study provides new insights into the regulation of human PINK1 and highlights the importance of PINK1 activation in the prevention of PD. The study also shows that PINK1 activation is dependent on the TOM complex and that the TOM complex is essential for PINK1 activation. The study also shows that PINK1 activation is important for the maintenance of mitochondrial function and the prevention of PD. The study provides a detailed understanding of the molecular mechanisms of PINK1 activation at the TOM complex and highlights the importance of PINK1 activation in the prevention of PD. The study also shows that PINK1 activation is essential for the elimination of damaged mitochondria through mitophagy. The study provides a detailed understanding of the molecular mechanisms of PINK1 activation at the TOM complex and highlights the importance of PINK1 activation in the prevention of PD.PINK1 is a key protein involved in the regulation of mitochondrial quality control and the prevention of Parkinson's disease (PD). Loss-of-function mutations in PINK1 are a common cause of early-onset PD. PINK1 is stabilized at the Translocase of Outer Membrane (TOM) complex of damaged mitochondria, which is essential for its activation. This study reports that co-expression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. The study systematically assessed the role of each TOM subunit in PINK1 activation and demonstrated that TOM20 and TOM70 are required for optimal PINK1 activation. The study also showed that TOM40 and its associated subunits TOM7 and TOM22 are essential for PINK1 activation. Structural modeling and mutagenesis studies revealed that the N-terminal and C-terminal extensions (NTE and CTE) of PINK1 interact with TOM20 and TOM70. These interactions are critical for PINK1 stabilization and activation at the TOM complex. The study also showed that TOM70 is required for optimal PINK1 stabilization and activation at the TOM complex. The findings suggest that PINK1 activation at the TOM complex is mediated by interactions with TOM20 and TOM70. These findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD. The study also showed that PINK1 activation is essential for the elimination of damaged mitochondria through mitophagy. The study provides new insights into the regulation of human PINK1 and highlights the importance of PINK1 activation in the prevention of PD. The study also shows that PINK1 activation is dependent on the TOM complex and that the TOM complex is essential for PINK1 activation. The study also shows that PINK1 activation is important for the maintenance of mitochondrial function and the prevention of PD. The study provides a detailed understanding of the molecular mechanisms of PINK1 activation at the TOM complex and highlights the importance of PINK1 activation in the prevention of PD. The study also shows that PINK1 activation is essential for the elimination of damaged mitochondria through mitophagy. The study provides a detailed understanding of the molecular mechanisms of PINK1 activation at the TOM complex and highlights the importance of PINK1 activation in the prevention of PD.