The Journal of Neuroscience, January 18, 2006, ():
Mitochondrial Encephalomyopathy in Drosophila
J. Neurosci. Celotto et al.
26: 810
Supplemental data
Files in this Data Supplement:
- supplemental material
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Supplemental Figure 1: Mutation in the mitochondrial ATP6 gene affects the F1F0 ATP synthase. (A) Direct sequence analysis of mutant and wild type mitochondrial genomes revealed exactly one mutation that was not polymorphic. The mutation, ATP6[1], is a G to A transition that alters a glycine (G) codon (GGA) to a glutamate (E) codon (GAA) at position 117 in the ATP6 gene. (B) Amino acid sequence alignment demonstrates the conservation of coding potential near the site of the mutation. Red boxes indicate a match with consensus. Orange boxes indicate a conservative substitution. The glycine at position 117 (blue asterisk, position 116 in humans) is invariant in all animals and separated by only six residues from a known human NARP mutation (W109R, black asterisk). (C) Secondary structure of ATP6, which contains 4 transmembrane helices (Yellow). Three human mutation sites known to cause NARP/MILS/FBSN diseases (red circles) and the fly mutation (pink circle) are indicated. (D) Schematic diagram of ATP6 as it is localized in the inner membrane (IM) of a mitochondrion. Residues numbered in blue denote the first and last residues in each helical segment, which are numbered (1-4). (E) Cartoon depicting the major structural features of the ATP synthase. F0 is composed of three different subunits types with a1b2c12 stoichiometry. The F1 is composed of five subunits with α3β3γ1δ1εstoichiometry. Figures adapted from reported structural data (Rastogi and Girvin, 1999; Schon et al., 2001). Species included in alignment are: A. quadrimaculatus (A. qu, NC_000875); Anopheles gambiae (A.ga, NC_002084); Drosophila mauritiana (D.ma, NC_005779); D. melanogaster (D.me, NC_001709); D. sechellia (D.se, NC_005780); D. simulans (D.si,NC_005781); D. yakuba (D.ya, NC_001322); and Homo sapiens (H. sa, NC_001807).
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Supplemental Figure 2: Neural dysfunction in the thoracic ganglion of ATP61 mutants. Longitudinal sections of two independent thoracic ganglia of day 7 ATP61;sesB1 (ANT1) mutants reveals significant neural degeneration that was not observed in wild type controls. sesB1 (ANT1) mutants manifest thoracic and brain neurodegeneration phenotypes at later time points (see Figures 2 and 3) demonstrating neural dysfunction in ATP61 accelerates the progressive degeneration of sesB1 in the thoracic ganglion. Animals were sacrificed, fixed in 2.5 % gluteraldehyde, paraffin embedded and serial 5 micron sections of the thorax were obtained and stained with H&E. n ≥ 8 animals per genotype per time point. Scale bar 100µm.
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Movie Supplement 1: Movie showing the individual slices from the tomogram of the ATP61 mitochondrion analyzed in Figure 7. The frames are displayed in sequence, such that one can “walk-through” the tomogram to get a sense of the 3-D organization of the membranes.
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Movie Supplement 2: Movie of an independent tomographic reconstruction of an ATP61 mitochondrion, confirming the salient features of the first reconstruction.
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Movie Supplement 3: Movie showing the membrane model of the tomogram in Figure 7 and Movie Supplement 1. Top and side views are shown in succession.
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Movie Supplement 4: Movie showing the individual slices from the tomogram of a wild type mitochondrion. The frames are displayed in sequence, such that one can “walk-through” the tomogram to get a sense of the 3-D organization of the membranes.
