Mitochondrial Fusion Promoter, M1

A cell-permeable phenylhydrazone compound that restores mitochondrial tubular network formation from the fragmented mitochondria seen in MEF lacking either one of the two outer mitochondrial membrane (OMM) mitofusins (EC₅₀ = 5.3 and 4.42 µM, respectively, in Mfn1 or Mfn2 knockout MEF cells) or MPP+-treated SH-SY5Y cells (5 µM 24 h), while displaying no effect on ER or lysosome morphology in Mfn1 knockout MEF. The effect of M1 is limited to enhancing weakened mitochondrial fusion machinery and M1 cannot by itself rebuild interconnected tubular mitochondria in MEF lacking both Mfn1/2 or the inner mitochondrial membrane (IMM) fusion mediator Opa1 (optic atrophy1). M1 (5 µM 24 h) is reported to boost the downregulated ATP5A and ATP5B protein level in either Mfn1 or Mfn2 knockout MEF to the wild-type MEF level and ATPase inhibitor oligomycin (Cat. No. 495455) at 5 µM is shown to completely offset the mitochondrial fusion effect by 5 µM M1 in Mfn1 knockout MEF. Both M1 and Z-VAD-FMK (Cat. No. 219007) are shown to protect SH-SY5Y against MPP⁺-induced neuronal toxicity and additive protection can be achieved via a combined treatment (62%, 73%, 77%, and 89% survival rate, respectively, with DMSO, 5 µM M1, 1 µM Z-VAD-FMK, and combined treatment). Comparing to mdivi-1 (Cat. No. 475856), M1 exerts its effect via promoting fusion rather than inhibiting fission or division.

A cell-permeable phenylhydrazone that restores mitochondrial tubular network formation in MEF lacking either of the two outer mitochondrial membrane (OMM) mitofusins (EC₅₀ = 5.3 and 4.42 µM, respectively, in Mfn1 or Mfn2 knockout MEF cells) or in MPP+-treated SH-SY5Y cells (5 µM 24 h), but not in MEF lacking both Mfn1/2 or the inner mitochondrial membrane (IMM) fusion mediator Opa1 (optic atrophy1). M1 (5 µM 24 h) is reported to boost the downregulated ATP5A & ATP5B protein level in Mfn1 or Mfn2 knockout MEF to the wild-type MEF level and ATPase inhibitor oligomycin (Cat. No. 495455) at 5 µM is shown to completely offset the mitochondrial fusion effect by 5 µM M1 in Mfn1 knockout MEF. Comparing to mdivi-1 (Cat. No. 475856), M1 exerts its effect via promoting fusion rather than inhibiting fission or division.

Cell permeable: yes

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Wang, D., et al. 2012. Angew. Chem. Int. Ed.51, 9302.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)