Supplemental Table 1 Toxicity Liver Kidney AST [IU/L] ref (54-269)   AST [IU/L] ref (54-269) ALT [IU/L] ref (26-77) BUN [mg/dL] ref (12-28) Control 8515 172 223 Met [1 mg/kg] 189117 3515 307 Mito-Met10 [1 mg/kg] 8916 2610 274

Supplemental Figure 1

Supplemental Figure 2

Supplemental Figure 3 A B C

Supplemental Figure 4 Mito-Met10 Dec-TPP+

Supplemental Figure 5 A Mito-Met2 B Mito-Met6 Day 0 Day 1 Day 2 Day 3 Control 0 M 12.5 M 25 M 50 M A Mito-Met2 Day 0 Day 1 Day 2 Day 3 Day 4 Day 6 Control 0 M 7.5 M 15 M 30 M B Mito-Met6

Supplemental Figure 6

Supplemental Figure 7

Supplemental Figure 8 Model setup Mito-Met10 Metformin MiaPaCa-2 PANC-1 OCR (% of control basal) HPNE IEC-6

Supplemental Figure 9 A B C

Supplemental Figure 10

Supplemental Figure 11