This section provides supplemental data supporting the main findings of the study on mitochondrial fusion and its role in protecting against neurodegeneration in the cerebellum. Key points include: 1. **Lethality of Meox2-Cre/Mfn1loxP Mice**: These mice show no abnormalities and have normal life spans. They were generated from various matings and examined over multiple generations. 2. **Rotarod Test with L7-Cre/Mfn2loxP Mice**: Cohorts of wild-type and mutant mice were tested weekly, with each mouse undergoing three trials. The results represent the average times ± standard deviation. 3. **Conditional Mfn1 and Mfn2 Knockouts**: Schematic diagrams and PCR genotyping confirm the successful targeting of Mfn1 and Mfn2 genes. Mitochondrial morphology in Mfn1loxP and Mfn2loxP MEFs is visualized using mitochondrially targeted EGFP. 4. **Degeneration of PCs in Meox2-Cre/Mfn2loxP and Wnt1-Cre/Mfn2loxP Mice**: Anti-calbindin immunofluorescence shows similar phenotypes to En1-Cre/Mfn2loxP mice, with stunted dendritic outgrowth and increased Purkinje cell loss with age. 5. **Electron Transport Compromise in Young L7-Cre/Mfn2loxP Mice**: COX and SDH staining of 6-week-old cerebella shows decreased COX activity and increased SDH activity in Purkinje cells without Mfn2 before Purkinje cell loss. 6. **Ultrastructure of Mfn1-Deficient PCs**: EM images of 7-week-old Meox2-Cre/Mfn1loxP cerebella and 9-week-old L7-Cre mice with Mfn1-/-, Mfn2+/+ genotypes show normal mitochondrial morphology and distribution. These supplementary materials provide detailed experimental data and visual evidence to support the main findings of the study.This section provides supplemental data supporting the main findings of the study on mitochondrial fusion and its role in protecting against neurodegeneration in the cerebellum. Key points include: 1. **Lethality of Meox2-Cre/Mfn1loxP Mice**: These mice show no abnormalities and have normal life spans. They were generated from various matings and examined over multiple generations. 2. **Rotarod Test with L7-Cre/Mfn2loxP Mice**: Cohorts of wild-type and mutant mice were tested weekly, with each mouse undergoing three trials. The results represent the average times ± standard deviation. 3. **Conditional Mfn1 and Mfn2 Knockouts**: Schematic diagrams and PCR genotyping confirm the successful targeting of Mfn1 and Mfn2 genes. Mitochondrial morphology in Mfn1loxP and Mfn2loxP MEFs is visualized using mitochondrially targeted EGFP. 4. **Degeneration of PCs in Meox2-Cre/Mfn2loxP and Wnt1-Cre/Mfn2loxP Mice**: Anti-calbindin immunofluorescence shows similar phenotypes to En1-Cre/Mfn2loxP mice, with stunted dendritic outgrowth and increased Purkinje cell loss with age. 5. **Electron Transport Compromise in Young L7-Cre/Mfn2loxP Mice**: COX and SDH staining of 6-week-old cerebella shows decreased COX activity and increased SDH activity in Purkinje cells without Mfn2 before Purkinje cell loss. 6. **Ultrastructure of Mfn1-Deficient PCs**: EM images of 7-week-old Meox2-Cre/Mfn1loxP cerebella and 9-week-old L7-Cre mice with Mfn1-/-, Mfn2+/+ genotypes show normal mitochondrial morphology and distribution. These supplementary materials provide detailed experimental data and visual evidence to support the main findings of the study.