Mitochondrial Fusion Promoter M1

使用Mitochondrial Fusion Promoter M1 has been used as a fusion promoter:to study its effects on peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α expression in breast cancer cellsto study the link between nucleoside diphosphate kinase 3 (NME3)-regulated mitochondrial fluctuations and stability of genome in NME3 knockdown cellsto study its effects on mitochondrial fusion in neuronal cells

一般的な説明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.