Zum Hauptinhalt springen
UB Hagen

Suchergebnisse

UB Katalog

Artikel & mehr
25 Treffer

Suchmaske

Suchtipp für den Bereich Artikel & mehr: Wörter werden automatisch mit UND verknüpft. Eine ODER-Verknüpfung erreicht man mit dem Zeichen "|", eine NICHT-Verknüpfung mit einem "-" (Minus) vor einem Wort. Anführungszeichen ermöglichen eine Phrasensuche.
Beispiele: (burg | schloss) -mittelalter, "berufliche bildung"

Das folgende Suchfeld wird hier nicht unterstützt: "Signatur / Strichcode".

Meinten Sie men?

Suchergebnisse einschränken oder erweitern

Aktive Suchfilter

25 Treffer

Sortierung: 
  2. Detailansicht für Treffer 2 öffnen
    Figure 2. Mfn is a specific target of VCP. ; (A) In fly thoraxes, VCP OE in wildtype (IFM-Gal4 control) and Mfn OE background results in a significant decrease in Mfn levels. Hsp60 was used as a mitochondria control; Actin was used as a loading control. (B) VCP RNAi leads to enhanced Mfn levels (1.72 ± 0.37 compared to wildtype, set as 1; p=0.021, independent t-test, N = 4). VCP RNAi results in accumulation of Mfn in the Mfn OE background (16.15 ± 0.85 as compared to Mfn OE alone, 9.02 ± 1.63, wildtype set as 1, p=0.0101, independent t test, N = 3). *p
    2017
    unknown
    Wie komme ich dran?
  3. Detailansicht für Treffer 3 öffnen
    Figure 3. VCP overexpression suppresses mitochondrial defects in PINK1 null, parkin null and parkin mul1 double null mutants. ; (A–E’) Compared to wildtype (A and A’), parkin and PINK1 mutants lose MitoGFP signal and accumulate large aggregates. VCP OE (IFM-Gal4>UAS-VCP) significantly rescues the MitoGFP phenotype in both mutants. Filamentous actin is stained with Rhodamine Phalloidin (Red). (A–E) Lower magnification. Scale bar: 20 µm. (A’–E’) Higher magnification. Scale bar: 5 µm. (A’’–E’’) Toluidine Blue shows that vacuole formation in the muscle tissue in parkin and PINK1 mutants is robustly suppressed by VCP OE. Thoraxes are assayed 2 days after eclosion. Scale bar: 30 µm. (A’’’–E’’’) At the ultrastructural level, wildtype (WT, IFM-Gal4 control) mitochondria are well aligned with compact cristae (A’’’). parkin and PINK1 mutants display swollen mitochondria with broken cristae (B’’’ and D’’’). VCP OE (IFM-Gal4>UAS-VCP) completely rescued the mitochondrial defects in both mutants (C’’’ and E’’’). Thoraxes are sectioned at 2 days after eclosion. Scale bar: 1 µm. (F) VCP OE caused a decrease in Mfn accumulation in parkin and PINK1 mutants. Mfn protein levels in the parkin mutant increased to 2.12 ± 0.69 as compared with wildtype (set as 1). VCP OE caused a decrease in Mfn levels in the parkin mutant to 1.26 ± 0.34 as compared with parkin (p=0.005, independent t test, N = 3. **pUAS-VCP) rescues the MitoGFP phenotype in parkin mul1 mutants (I and I’). Myofibrils are stained with Rhodamine Phalloidin (Red). (G–I) Lower Magnification, Scale bar: 20 µm; (G’–I’) Higher Magnification, Scale bar: 5 µm. (J) Expression pattern of EDTP-Gal4 and IFM-Gal4 in 3-day-old flies. EDTP-Gal4 driven UAS-MitoGFP signal is barely detected in the thorax, where the indirect flight muscle is located, suggesting that EDTP-Gal4 does not have sufficient flight muscle specific expression. MitoGFP is present at high levels in the thoraxes of IFM-Gal4 driven flies. Thorax structure is outlined with dashed white lines in white light and indicated with a white arrowhead in GFP field. (K) Schematic diagram showing that PINK/Parkin in parallel with Mul1 negatively regulates Mfn protein levels; VCP negatively regulates Mfn protein levels independent of these modifiers.
    2017
    unknown
    Wie komme ich dran?
  6. Detailansicht für Treffer 6 öffnen
    Figure 1. Endogenous VCP regulates mitochondrial fusion via negative regulation of Mfn protein levels. ; (A–C) MitoGFP localization to mitochondria serves as a marker for healthy mitochondria and their morphology in the indirect flight muscle. VCP overexpression (VCP OE, B) results in small mitochondria compared to wildtype (WT) flies (A); VCP RNAi expression results in elongated mitochondria (C). Scale Bar: 5 µm. (A’–C’’) Electronic microscopic (EM) images show that VCP OE (B’–B’’) results in smaller mitochondria as compared with WT (A’–A’’). VCP RNAi generates elongated mitochondria with intact cristae (outlined with white dashed lines in C’ and C’’). (A’–C’) Lower magnification; (A’’–C’’) Higher magnification of mitochondria outlined with black solid lines in A’–C’. Scale bar: 1 µm. (D): Schematic diagram of nurse cell mosaic analysis in Drosophila female germline. A stage 10A egg chamber has three types of cells. The monolayer follicle cells coat the surface of the egg chamber; 15 nurse cells provide proteins and RNAs to the oocyte during oogenesis. Heat shock induction of mitotic recombination during larvae stages results in the creation of a mosaic pattern in the adult nurse cells. Ubi-mRFP.NLS (Red) is used as a clone marker. Wildtype (WT) cells are labeled with two copies of RFP, +/+; heterozygous mutant cells have one copy of RFP and one copy of vcp loss-of-function mutant, vcpK15502/+; homozygous mutant cells are RFP negative and have two copies of vcp loss-of-function mutant, vcpK15502/vcpK15502. (E): A stage 10A egg chamber with a mosaic pattern of nurse cells. Red signal is Ubi-mRFP.NLS. Scale bar: 20 µm. (E’) Anti-ATP5A antibody staining is used to visualize mitochondrial morphology in nurse cells. Scale bar: 20 µm. (F–I) Higher magnification view of mitochondrial morphology in E’ (outlined in white solid lines). Mitochondria appear as discrete and punctate structures in wildtype (G) and heterozygous vcp mutant cells (F), but becomes elongated and clumped in homozygous vcp loss-of-function mutant cells (H and I). Scale bar: 5 µm. (J) A stage 10B egg chamber with a mosaic pattern of nurse cells. Red signal is Ubi-mRFP.NLS; Green signal is anti-GFP staining of pCasper-Mfn-eGFP. Scale bar: 20 µm. (J’–J’’) Higher magnification of the egg chamber in J (outlined in white solid lines). Wildtype cells are RFP positive and homozygous vcp loss-of-function mutant cells are RFP negative (J’). pCasper-Mfn-eGFP levels significantly increase in homozygous vcp loss-of-function mutant cells (J’’). Scale bar: 10 µm.
    2017
    unknown
    Wie komme ich dran?
  7. Detailansicht für Treffer 7 öffnen
    Figure 5. VCP disease mutants are hyperactive in downregulating Mfn protein levels and inhibiting mitochondrial fusion. ; (A–B’) Electronic microscopic images of muscle of different genotypes. Compared to WT (IFM-Gal4 control, A and A’), mitochondria are smaller with intact cristea in VCP WT (B and B’) 6 days after eclosion. Scale bar: 1 µm. (C–E’) Expression of VCP RH and AE leads to distorted fiber structure, and small mitochondria with broken or empty cristae. mfn RNAi flies have similar morphological defects in mitochondria (E and E’). Scale bar: 1 µm. (F) Expression of VCP RH and AE lead to a further reduction in Mfn as compared to VCP WT. Mfn levels in VCP WT are reduced to 0.73 ± 0.21 as compared with Gal4 control, which is set as 1 (p=0.037, independent t test, N = 3). Mfn levels in VCP RH and AE are reduced to 0.52 ± 0.14 (p=0.037, independent t test, N = 3) and 0.32 ± 0.16 (p=0.003, independent t test, N = 3) as compared with Gal4 control. Mfn levels are normalized with those of Hsp60, a mitochondria marker. Expression of VCP ATPase defective mutant E2Q (p=0.097, independent t test, N = 3) does not significantly change the Mfn level in fly thoraxes as compared with Gal4 control. n.s.: no statistical significance, p>0.05. Normalized Mfn levels are shown as mean±½SD. (G–L) MitoGFP localization assay shows expression of VCP WT (H), RH (I) and AE (J) potently rescues the mitochondrial defects in parkin mutant (G). Expression of the ATPase defective mutant E2Q (K) or VCP RNAi (L) does not. Scale bar: 20 µm. (M–R) MitoGFP assay shows expression of VCP WT (N), RH (O) and AE (P) potently rescues the mitochondrial defects in parkin mul1 double mutants (M). Expression of VCP E2Q (Q) and VCP RNAi (R) do not. Scale bar: 20 µm. (S) Western blot shows that increased Mfn levels normally present in a parkin null mutant are significantly decreased in VCP WT, RH and AE flies, but not in VCP E2Q flies. Mfn levels are further decreased in a parkin mutant expressing VCP RH (p=0.0228, independent t test, N = 3) or AE (p=0.00565, independent t test, N = 3), as compared to VCP WT. Samples are from 2-day-old fly thoraces. Normalized Mfn levels are shown as mean±½SD. *p
    2017
    unknown
    Wie komme ich dran?
  8. Detailansicht für Treffer 8 öffnen
    Figure 4. Expression of VCP disease mutants and mfn RNAi knocking down lead to pathology in adult muscle tissue. ; (A) Diagram of Human p97/VCP protein domains and two disease mutants, VCP R155H and A232E. Their corresponding Drosophila homologues are VCP R152H and A229E, hereafter referred to as VCP RH and AE. (B) Expression levels of UAS-VCP WT, RH and AE disease mutants expressed under IFM-Gal4 are comparable. (C) Diagram of Drosophila indirect flight muscle structure. Mitochondria (Green) and nuclei (Orange) are densely packed in between myofibrils (which contain large amounts of actin, Black). (D–D''') MitoGFP (Green) and TUNEL staining (Red). 6-day-old WT (IFM-Gal4 control) flies and VCP WT flies have healthy muscles (no TUNEL staining) and are MitoGFP positive (D and D'). 6-day-old VCP RH and AE expressing flies show high levels of TUNEL staining. 97 ± 3.6% and 95.7 ± 5.1% of RH (p=0.03. RH v.s. WT, independent t test) and AE (p=0.015, AE v.s. WT, independent t test) and are MitoGFP negative (D'' and D'''). Scale bar: 10 µm. (E–E''') Toluidine Blue staining of muscle in WT, VCP WT, RH and AE flies. Myofibrils are well aligned with densely packed mitochondria in WT and VCP WT flies 6 days after eclosion (E and E'). In VCP RH and AE flies fiber structure is disrupted, and mitochondria are misaligned and lightly stained, with empty spaces in between (E'' and E'''). Scale bar: 40 µm. (F–F''') Anti-TDP43 antibody staining shows nuclear (white arrowhead) and sarcoplasmic localization of TDP-43 in WT and VCP WT adult fly muscle (F and F'). In VCP RH and AE flies the nuclear signal disappears and the signal is increased in muscle sarcoplasm (F'' and F'''). Scale bar: 5 µm. (G–G''') Anti-Ref(2)P/p62 antibody staining. The signal is weak and uniform in WT and VCP WT flies (G and G'), and punctate in VCP RH and AE flies (G'' and G'''). Scale bar: 5 µm. (H–H''') Anti-P4D1 ubiquitin antibody staining. Signal is weak and uniform in WT and VCP WT flies (H' and H'), and punctate in VCP RH and AE flies (H'' and H'''). Scale bar: 5 µm. (I–M) Effects of mfn RNAi in 8-day-old adult muscle tissue. (I–M) Wildtype muscle visualized with TUNEL and mitoGFP (I), anti-TDP43 (J), Toluidine blue (K), anti-p62 (L), and anti-ubiquitin (M). (I'–M') mfn RNAi muscle visualized with the same probes as above. Scale bar: 30 µm in K-K’, 5 µm in the rest.
    2017
    unknown
    Wie komme ich dran?
  9. Detailansicht für Treffer 9 öffnen
    Figure 5—figure supplement 2. Mfn expression can suppress mitochondrial defects observed in VCP RH and AE flies. ; (A) 2 copies of genomic rescue Mfn-HA (pCasper-Mfn-HA) lead to a heterogeneous mitochondrial phenotype in which some mitochondria are elongated. A’ shows a typical elongated mitochondrion. (B–E’) In 2-day-old flies, expression of 2 copies pCasper-Mfn-HA (C, C’ and E, E’) results in suppression of mitochondrial defects (fragmented mitochondria with abnormal cristae) in VCP RH (B and B’) and AE (D and D’) flies. Scale bar: 1 µm.
    2017
    unknown
    Wie komme ich dran?
  10. Detailansicht für Treffer 10 öffnen
    Figure 5—figure supplement 1. Expression of VCP disease mutants leads to small mitochondria with abnormal cristae, phenotypes similar to mfn RNAi knocking down. ; (A–B’) 2 days after eclosion, EM shows that compared to WT (IFM-Gal4 control, A and A’), VCP WT expression results in smaller mitochondrial with intact cristae (B and B’). (C–E’) VCP RH and AE also have smaller and fragmented mitochondria, but the cristae are abnormal (C–D’), similar to the phenotype of mfn RNAi flies (E and E’). Scale bar: 1 µm.
    2017
    unknown
    Wie komme ich dran?
  11. Detailansicht für Treffer 11 öffnen
    Figure 5. p97 governs ER-OMM contact via the extraction of Mfn2 complexes. ; (A) Immunoblot analysis of NP-40-solubilized mitochondria, isolated from U2OS:GFP-parkin WT cells treated with 20 μM CCCP for the indicated time, separated by blue native- (BN-) and SDS-PAGE. (B, C) Immunoblot analysis of Mfn1- (B) and Mfn2- (C) containing complexes in NP-40-solubilized mitochondria, isolated from U2OS:GFP-parkin WT and C431S cells treated with 20 μM CCCP for four hours, separated by BN- and SDS-PAGE. (D) Mitochondria isolated from U2OS:GFP-parkin WT cells treated with 20 μM CCCP for one hour were, after solubilization in NP-40, incubated with 1 μM Usp2 for 30 min at 37°C prior to separation by SDS-PAGE. Red asterisks indicate ubiquitinated species of Mfn1 and Mfn2. Densitometry calculations for the Mfn1 and Mfn2 bands (shorter exposure) relative to CIII-core2 are shown under the respective immunoblots. (E) Immunoblot analysis of NP-40-solubilized mitochondria, isolated from U2OS:GFP-parkin WT cells treated with 20 μM CCCP in the presence or absence of 25 μM NMS-873 for the indicated time, separated by blue native- (BN-) and SDS-PAGE. Red asterisks indicate ubiquinated Mfn species visible by SDS-PAGE, while the arrowhead denotes the unmodified band. (F) Representative TEM images of mitochondria in contact with ER (pseudocoloured blue) in U2OS:GFP-parkin cells treated with 20 μM CCCP (‘+CCCP’) for four hours in the presence or absence of 25 μM NMS-873. Scale bar, 500 nm. (G,H) Quantification of TEM from (F) in cells treated with (blue bars) or without (red bars) 20 μM CCCP for four hours. The percent of OMM per mitochondrion (G) and mitochondria per field (H) in contact with the ER was quantified. Bars represent mean ± SEM, n = 99 to 187 mitochondria in 12 to 14 fields per condition. n.s., not significant; *, p
    2018
    unknown
    Wie komme ich dran?
  12. Detailansicht für Treffer 12 öffnen
    Figure 3—figure supplement 3. Parkin recruitment kinetics in cells lacking both Mfns and other mitochondria-ER tethering factors. ; (A) Immunoblot analysis of whole-cell lysates from cells cultured in glucose or galactose transfected with control siRNA or siRNA targeting Mfn1 (‘siMfn1’), Mfn2 (‘siMfn2’) or both mitofusins (‘siMfn1 +2’). (B) Representative confocal images of GFP-parkin recruitment to mitochondria as a function of time in U2OS:GFP-parkin cells treated with 20 μM CCCP. Red asterisks indicate cells in which GFP-parkin has fully translocated to mitochondria. Scale bar, 20 microns. (C) Quantification of parkin recruitment in cells from (B). Data points represent mean ± SEM, n = 3 replicates cells per condition, with >100 cells counted per condition for each replicate. (D) Parkin recruitment at one hour CCCP in cells from (B) arranged as a histogram. Bars represent mean ± SEM. n.s., not significant; *, p100 cells counted per condition for each replicate. (I) Parkin recruitment at one hour CCCP in cells from (G) arranged as a histogram. Bars represent mean ± SEM. n.s., not significant; **, p
    2018
    unknown
    Wie komme ich dran?
  13. Detailansicht für Treffer 13 öffnen
    Figure 5—figure supplement 3. Mfn expression does not significantly rescue the pathology in VCP RH and AE fly muscles. ; 2 copies of the pCasper-Mfn-HA/eGFP transgene in VCP RH and AE flies at 6 days of age does not significantly alter muscle cell death assayed by TUNEL/MitoGFP (A, A’ and F, F’, Scale bar: 10 µm), overall tissue disintegration (B, B’ and G, G’, Scale bar: 40 µm), TDP43 mislocalization (C, C’ and H, H’ Scale bar: 5 µm), or the frequency of p62 (D, D' and I, I', Scale bar: 5 µm) and ubiquitin positive aggregates (E, E’ and J-J’, Scale bar: 5 µm).
    2017
    unknown
    Wie komme ich dran?
  14. Detailansicht für Treffer 14 öffnen
    Figure 7. VCP inhibitors promote mitochondrial elongation. ; (A–A’’) MitoGFP assay for mitochondrial morphology. Compared to DMSO-fed flies, 10 µM NMS-873 or ML240 feeding results in more fused mitochondria in 2-day-old flies. Scale bar: 5 µm. (B–B’’ and C–C’’) In 6-day-old flies fed with 30 µM NMS-873 (B’) or 30 µM ML240 (B’’), elongated mitochondria (outlined in dashed white lines) are observed in muscle. Mitochondria are small in VCP WT flies (C) as compared with WT (IFM-Gal4 control, B). This phenotype is reversed by 30 µM NMS-873 (C’) or 30 µM ML240 (C’’) feeding and shifted towards a pro-fusion direction, as the mitochondria are also elongated as compared with WT (B). (B’’’ and C’’’) Statistical analysis of mitochondrial size in EM cross sections. In wildtype flies, 30 µM NMS-873 or ML240 feeding results in a mitochondrial size increase to 6.46 ± 0.44 µm2 (p=0.007, independent t test, N = 45) or 5.75 ± 0.48 µm2 (p=0.032, independent t test, N = 39) as compared to the DMSO group (3.45 ± 0.27 µm2, N = 47). VCP WT expression results in small mitochondria (1.78 ± 0.05 µm2, N = 68) as compared with WT (B). Feeding of 30 µM NMS-873 (5.41 ± 0.40 µm2, p=0.000, independent t test, N = 44) or ML240 (4.90 ± 0.42 µm2, p=0.000, independent t test, N = 45) reverses these effects. Mitochondria size is shown as mean±½SEM. (D) pCasper-Mfn-eGFP levels accumulate in a dose dependent manner when treated with NMS-873 at 0.5 µM and 1 µM for 14 hr.
    2017
    unknown
    Wie komme ich dran?
  16. Detailansicht für Treffer 16 öffnen
    Figure 3. Mitophagy under OXPHOS-inducing conditions requires FIS1, TBC1D15, and p62. ; (A) Mitophagy in cells with mutations in mitochondrial dynamics genes. MEFs of the indicated genotype were cultured in glucose or acetoacetate medium, and mitophagy was quantified using the Cox8-EGFP-mCherry marker. Neither Mfn-dm cells nor Opa1-/- cells were viable in acetoacetate-containing medium. Error bars indicate SD of three biological replicates, p=0.0078 (Student’s t-test. (B) MEFs stably expressing Cox8-EGFP-mCherry were grown in acetoacetate containing medium and then imaged by fluorescence microscopy. p62 and Tbc1d15 shRNAs were introduced by retroviral infection. (C) Co-localization of mTurquoise2-LC3B with mitochondria. MEFs were grown in acetoacetate containing medium. Note that mTurquoise2 puncta localize to mitochondrial puncta (arrows) only in WT cells. (D) Co-localization of P62 with mitochondria. MEFs were grown in acetoacetate containing medium and immunostained with anti-P62 (green) and anti-HSP60 (red). (E) Quantification of red-only puncta in WT cells and cells containing shRNA against Tbc1d15 or p62 cultured in glucose (Glu) or acetoacetate (Ac) medium. Error bars indicate SD of three biological replicates, p=0.0048 (Tbc1d15), p=0.0053 (p62) (Student’s t-test).
    2016
    unknown
    Wie komme ich dran?
  18. Detailansicht für Treffer 18 öffnen
    Figure 4. Generation and expression of the IFM-GAL driver; mfn overexpression, but not loss of drp1, induces PINK1/parkin-mutant like pathology. ; (A–J) Different developmental stages of flies expressing GFP under Mef2-Gal4 (A–E) or IFM-Gal4 (F–J). (A) Third instar larvae show GFP expression in whole body muscles. (B) At the early pupal stage, GFP is expressed in a similar pattern as in larvae. However, the GFP expression pattern become more specific at the late pupal stage (C), in which the strongest GFP signal is seen in the thorax, and a weaker signal is observed in the head and abdomen (arrows). (D) In an adult fly, dorsal view shows GFP signal in the thorax, upper abdomen and legs. (E) GFP is also expressed in adult head and legs, marked with arrows. (F) Flies expressing GFP under IFM-Gal4 show no GFP expression in third instar larvae, or in early pupae (G). (H) GFP is strongly expressed only in the thorax at the late pupal stage, but not in other areas (arrows). (I) In the adult fly, GFP signal is highly concentrated in the thorax. No GFP expression in abdomen and legs is observed, arrows. (J) In contrast to GFP expression under Mef2-Gal4, IFM-Gal4 does not express in adult head or legs, as indicated with arrows. (K–P, T–Y) Confocal images of muscle double labeled with mitoGFP (green) and phalloidine (red) (K–M, T–V), or those labeled with mitoGFP and TUNEL (red) at lower magnification (N–P, W–Y), respectively. (Qa–Sb) EM images of mitochondria in muscle. Single mitochondrion from the black-boxed area in Qa, Ra, Sa is shown in Qb, Rb, Sb. Scale bars: 1 µm (Qa, Ra, Sa) and 0.5 µm (Qb, Rb, Sb). Compared with wild-type (K and N), parkin null mutant (L and O) shows overall reduced levels of mitoGFP signal, large mitochondrial clumps, and muscle cell death. Similar phenotypes are observed with mfn overexpression (M and P), and these phenotypes are suppressed by MUL1 overexpression (T and W). As a control, parkin overexpression also suppresses phenotypes due to mfn overexpression (U and X). Importantly, drp1 null (drp11/drp12) mutant muscle does not have any mitochondrial clumping or TUNEL-positivity seen in loss of parkin function or mfn overexpression (V and Y). mfn overexpression is driven by IFM-Gal4. Scale bars: 5 µm.
    2014
    unknown
    Wie komme ich dran?
  19. Detailansicht für Treffer 19 öffnen
    Figure 9. Models for how MUL1 interacts with PINK1/parkin. ; (A) Schematic depictions of how MUL1, PINK1, Parkin, and Mfn interact in the mitochondria. In mammalian cells, upon mitochondrial damage (CCCP or antimycin A treatment), PINK1 is stabilized onto the mitochondrial OM of damaged mitochondria, with its kinase domain facing the cytosol (Zhou et al., 2008). PINK1 recruits Parkin onto the OM, either through direct phosphorylation or indirect interaction with other proteins (not depicted here) (Jin and Youle, 2012). Parkin then ubiquitinates multiple substrates on the OM, including Mfn. MUL1, a mitochondrial OM-anchored ligase with its RNF domain facing the cytosol, also mediates ubiquitination of Mitofusin. (B) The PINK1/parkin pathway and MUL1 act in parallel to regulate mfn, and maintain mitochondrial function and tissue health. Reducing either PINK1/parkin or MUL1 leads to increased levels of Mfn. Significant elevation of Mfn leads to mitochondrial dysfunction and tissue damage, similar to what is observed in PINK1/parkin mutants. Loss of both PINK1/parkin and MUL1 leads to significantly higher Mfn levels, associated with severe mitochondrial dysfunction and tissue damage. OM: mitochondrial outer membrane; IM: mitochondrial inner membrane.
    2014
    unknown
    Wie komme ich dran?
  20. Detailansicht für Treffer 20 öffnen
    Figure 5. MUL1 acts in parallel to the PINK1/parkin pathway. ; (A–H) Images of thoraces of various mutants. Arrows point to thoracic indentations due to muscle degeneration. PINK1 MUL1 and parkin MUL1 double mutants have more severe thoracic indentation compared to either mutant alone. Remarkably, the severe thoracic indentation phenotype in parkin MUL1 double mutants is almost completely suppressed when mfn is also knocked down. (I–P) Mitochondria are labeled using an anti-ATP synthase antibody in the IFM. While PINK1, parkin, and MUL1 mutant show slightly elongated mitochondrial morphology, PINK1 MUL1 and parkin MUL1 double mutants exhibit highly elongated and interconnected mitochondria. These phenotypes can be suppressed by mfn knockdown. Instead of using mitoGFP, we utilized anti-ATPase antibodies that allow better visualization of the enhancement phenotypes seen with double mutants. (Q) Relative ATP levels in whole flies of various mutants (mean ±SEM from three experiments, five 5-day-old flies for each genotype). ** and *** significantly different from wild-type, p
    2014
    unknown
    Wie komme ich dran?
xs 0 - 576
sm 576 - 768
md 768 - 992
lg 992 - 1200
xl 1200 - 1366
xxl 1366 -