Fig 2: Opti-ELF-WMF suppressed the activities of the mitochondrial electron transport chain (ETC) complex II.a Relative enzymatic activities of mitochondrial ETC complex I, II, III, and IV of mouse liver homogenates exposed to Opti-ELF-WMF in vitro for 8 min (mean ± SD, n = 3 to 6 mice each; **q < 0.01 by multiple Student’s t-tests). b Fractional and extended ETC complex II activities (succinate:quinone reductase [SQR], succinate-cytochrome c reductase [SCR], succinate dehydrogenase [SDH], succinate dehydrogenase flavoprotein subunit [SDHA]) of isolated mitochondria exposed to Opti-ELF-WMF in vitro for 8 min (mean ± SD, n = 4 mice each; ****q < 0.0001 by multiple Student’s t-tests). See e for a schematic of the fractional enzymatic activities. c Mitochondrial mass (MitoTracker Green) of AML12 cells treated with variable concentrations of a mitochondrial ETC complex II inhibitor, 3-nitropropionic acid, exposed to Opti-ELF-WMF in cellulo (mean ± SD, n = 3 culture dishes each; **q < 0.01 and ***q < 0.001 by multiple Student’s t-tests). d Mitochondrial mass (MitoTracker Green) of AML12 cells treated with variable concentrations of a mitochondrial ETC complex I inhibitor, rotenone, exposed to Opti-ELF-WMF in cellulo (mean ± SD, n = 3 culture dishes each; *q < 0.05, and **q < 0.01 by multiple Student’s t-tests). e Schematic to indicate the fractional and extended enzymatic activities of mitochondrial ETC complex II measured in b. Complex II is composed of SDHA, SDHB, SDHC, and SDHD. See also Fig. S5.

Fig 3: Conservation of SDHB and its mutation in heritable cancer. (A) Clustal W multiple alignment shows that C. elegans SDHB-1 has 60% identity and 84% similarity to the human homolog (identical or similar residues highlighted in blue and light blue, respectively). Three cysteine motifs characteristic of conserved iron-sulfur clusters are underlined. The boxed area and arrow indicate the critical Arg230 position. (B) Pedigree carrying mutated Arg230His SDHB, the mutation that can lead to pheochromocytoma/paraganglioma. Individual I.4 died of disseminated malignancy. Individuals I.2 (age 70) and I.3 (age 74) are tumor free; II.6 and II.7 (both 39, non-identical twins) each have tumors. (C) Genomic structure of the sdhb-1 region and gk165 deletion (dashed red lines indicate the deleted 2198 bp, including the first five exons of sdhb-1 and the first and partially the second exon of the neighboring gene, cup-15). We also analyzed a transgenic strain (see Results) containing a missense mutation G1647A in the genomic sequence (G731A in the cDNA) resulting in Arg244His.