219315-22-7

M-1 (219315-22-7) enhances mitochondrial fusion without interfering with endoplasmic reticulum (ER) and lysosome morphology.1 M-1 protects cells from mitochondrial fragmentation-associated cell death.2 Promotion of mitochondrial fusion has protective effects in rotenone-induced neurotoxicity.3 Cell permeable.

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 cells
• to study the link between nucleoside diphosphate kinase 3 (NME3)-regulated mitochondrial fluctuations and stability of genome in NME3 knockdown cells
• to study its effects on mitochondrial fusion in neuronal cells

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.

Cell permeable: yes

Store at -20°C

Andreaux et al. (2013), Pharmacological approaches to restore mitochondrial function; Nature Rev. Drug Disc., 12 465 Yang et al. (2015), Mitochondrial fusion provides an ‘initial metabolic complementation’ controlled by mtDNA; Cell Mol. Life Sci., 72 2585 Peng et al. (2017), The interaction of mitochondrial Biogenesis and Fission/Fusion Mediated b PGC-1a Regulates Rotenone-Induced Dopaminergic Neurotoxicity; Neurobiol., 54 3783