Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: CoQ10 is associated with the dnm1l gene. a-g Network pharmacology analysis composed of target gene prediction ( a ), protein–protein interaction (PPI) ( b ), Gene Ontology-cellular components (GO-CC) ( c ), Gene Ontology-biological processes (GO-BP) ( d ), Gene Ontology-molecular function (GO-MF) ( e ), Kyoto Encyclopedia of Genes and Genomes (KEGG) ( f ) and target gene prediction in GSEA database ( g ). Network pharmacology analysis elucidated the correlation between Drp1 deficiency and CoQ10 supplementation

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques:

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: Long-term administration of CoQ10 effectively prevents working memory deficits and cerebellar inflammation. a Time line of the experiment. PC-Drp1 −/− mice received long-term CoQ10 supplementation or vehicle (PC-Drp1 −/− + Veh) in drinking water from postnatal day 15 to day 90. b Traces in the eight-arm maze test. c Quantitative analysis of working memory errors in the eight-arm maze test, n = 5 or 6 mice. d Quantitative analysis of food searching strategies, n = 5 or 6 mice. e Immunofluorescence images and analysis of Iba1 (microglia marker) expression in 1M/2M/3M PC tdTomato -Drp1 −/− mice, with 2M PC tdTomato mice serving as the control group. Scale bars, 50 µm, n = 3 mice. f Western blot analysis for Iba1 in 3M PC-Drp1 −/− mice and 3M Pcp2 Cre control mice, n = 3 mice. g Immunofluorescence images and quantitative analysis of Iba1 (green) expression in PCs (red) of PC tdTomato -Drp1 −/− + CoQ10 group and PC tdTomato -Drp1 −/− + Veh group. Scale bars, 20 µm, n = 3 mice. Mean ± SD, two-way ANOVA ( c ), one-way ANOVA ( d and e ) and unpaired two-tailed t -test ( f and g )

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Immunofluorescence, Marker, Expressing, Control, Western Blot, Two Tailed Test

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: CoQ10 treatment prevents impairment of PC structure induced by Drp1 deletion. a Golgi staining images of PCs in PC-Drp1 –/– with long-term CoQ10 supplementation or vehicle. Scale bar, 50 µm. b Quantitative analysis of the complexity of PCs, n = 3 mice. c Golgi staining images of PC dendrite abundance in PC-Drp1 –/– + CoQ10 group and PC-Drp1 –/– + Veh groups. Scale bar, 10 µm. d, e Quantitative analysis of the density of PC dendritic spines ( d ) and dendritic branch length ( e ), n = 3 mice. f Immunofluorescence images of PSD95 expression in PC tdTomato -Drp1 –/– + CoQ10 and PC tdTomato -Drp1 –/– + Veh groups. Scale bars, 20 µm. g Confocal microscopy images of tdTomato-positive cells (PCs) in PC tdTomato -Drp1 –/– + CoQ10 group and PC tdTomato -Drp1 –/– + Veh group. Scale bars, 500 µm. h–o Quantitative results of PC density in lobules II–X, n = 3 mice. Mean ± SD, unpaired two-tailed t -test ( b , d and e ) and one-way ANOVA ( h – o ). ns, no significance

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Staining, Immunofluorescence, Expressing, Confocal Microscopy, Two Tailed Test

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: CoQ10 ameliorates memory impairment in DRP1-deficient mice by binding to Coa6. a Proteomic identification and analysis by Orbitrap HF-X LC–MS/MS high-resolution mass spectrometry. HFX was used for mass spectrometry signal acquisition (with a 70-min time gradient for each sample), n = 3 mice. b Differential gene analysis between the 10 μM and 100 μM CoQ10 groups and their respective control groups . c The intersection of the two groups of heat-resistant proteins was analyzed. d PET28A-Coa6 was constructed into the prokaryotic expression vector PET28A by homologous recombination method. e – g Qualitative analysis of Coa6 content by CETSA ( e ), DARTS ( f ), and surface plasmon resonance ( g ), n = 3 mice. h The structure of the Coa6-CoQ10 complex was predicted using ProtENIX. In this three-dimensional schematic diagram, orange-marked regions denote negatively charged binding sites, bluish violet regions denote positively charged binding sites, and purple arrows indicate directional hydrogen bonding with the arrow tail representing the hydrogen bond donor and the arrowhead pointing to the hydrogen bond acceptor. These three types of molecular interactions collectively constituted key binding elements at the CoQ10-Coa6 interaction interface. The red dotted box shows that the methoxy group of CoQ10 forms a hydrogen bond with the lysine residue at position 18 (K18) of Coa6, while its extended hydrophobic tail engages in hydrophobic interactions with residues including Tryptophan at position 59 (W59), Valine at position 45 (V45), and Proline at position 35 (P35), the 36th Valine (V36), the 94th Tryptophan (W94), the 97th Tyrosine (Y97), the 98th Phenylalanine (F98), the 104th Tyrosine (Y104), the 107th Phenylalanine Residues (F107) of Coa6. i Western blot analysis for Coa6 in the cerebellar cortex of Control, PC-Drp1 −/− + CoQ10 mice and PC-Drp1 −/− + Veh mice, n = 3 mice. Mean ± SD, one-way ANOVA ( i )

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Binding Assay, Liquid Chromatography with Mass Spectroscopy, Mass Spectrometry, Control, Construct, Expressing, Plasmid Preparation, Homologous Recombination, SPR Assay, Residue, Western Blot

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: CoQ10 ameliorates Drp1 deficiency-induced mitochondrial membrane instability and ETC dysfunction. a Confocal microscopy images of GFP-positive cells (PCs) in PC Mito -Drp1 −/− mice with long-term CoQ10 or vehicle treatment. Images following MiNA treatment are also provided. Scale bars, 50 µm. b Quantitative analysis of the individual mitochondrial number, mitochondrial network, mitochondrial network branch length, and mean branch quantity of the mitochondrial network in PC Mito -Drp1 −/− + CoQ10 group and PC Mito -Drp1 −/− + Veh group, n = 3 mice. c Mitochondrial ultrastructure by transmission electron microscopy. Scale bars, 0.5 µm (upper) and 0.2 µm (lower). d Quantitative analysis of mitochondrial perimeter, area, circularity, and cristae abundance, n = 3 mice. e Quantitative analysis of mitochondrial membrane potential (MMP) results by JC-1 detection of the purified mitochondria from the cerebellar cortex of PC-Drp1 −/− + CoQ10 mice and PC-Drp1 −/− + Veh mice, n = 6 mice. f Western blot analysis for mitochondrial OXPHOS complexes I (NDUFB8), II (SDHB), III (UQCRC2), IV (MTCO1), and V (ATP5A), in the cerebellar cortex of PC-Drp1 −/− + CoQ10 mice and PC-Drp1 −/− + Veh mice, n = 3 mice. * P < 0.05. g-j Western blot analysis for COX4 ( g, h ), SOD1 ( i ) and GPx1 ( j ) in PC-Drp1 −/− + CoQ10 mice and PC-Drp1 −/− + Veh mice, n = 3 mice. k ROS results and quantitative analysis by DCFH-DA detection of the cells isolated from the cerebellar cortex of PC-Drp1 −/− + CoQ10 mice and PC-Drp1 −/− + Veh mice, n = 5 mice. Mean ± SD, unpaired two-tailed t -test ( b , d – f and h–k )

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Membrane, Confocal Microscopy, Transmission Assay, Electron Microscopy, Purification, Western Blot, Isolation, Two Tailed Test

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: Down-regulation of Coa6 abolishes the therapeutic efficacy of CoQ10 in Drp1-deficient mice. a Schematic of the experimental design for Drp1-deficient mice after Coa6 down-regulation. b , c Multiple immunohistochemical images ( b ) and quantification ( c ) of Coa6 expression in the PCs. Scale bars, 20 µm. n = 3 mice. d Traces in the eight-arm maze test. e Quantitative analysis of working memory errors, n = 6 mice. f Quantitative analysis of percentages of different strategy angles, n = 6 mice. * P < 0.05 . g, h Multiple immunohistochemical images ( g ) and quantification ( h ) of PSD95 expression in the PCs. Scale bars, 20 µm. n = 3 mice. i-l Western Blot analysis of the expression levels of mitochondrial OXPHOS complexes ( i ), COX4 ( j ), GPX1 ( k ), and SOD1 ( l ) in the cerebellum, n = 3 mice. ** P < 0.01, *** P < 0.001 . m Quantitative analysis of ROS results using DCFH-DA detection in the cerebellum, n = 6 mice. n Quantitative analysis of mitochondrial membrane potential (MMP) results by JC-1 detection in the cerebellum, n = 6 mice. o Quantitative analysis of ATP results in the cerebellum, n = 6 mice. Mean ± SD, unpaired two-tailed t -test ( c , f , h–o ) and two-way ANOVA ( e )

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Drug discovery, Immunohistochemical staining, Expressing, Western Blot, Membrane, Two Tailed Test

Journal: Translational Neurodegeneration

Article Title: The Drp1-CoQ10-Coa6-ETC axis represents a therapeutic potential for working memory impairment caused by neuronal mitochondrial dysfunction

doi: 10.1186/s40035-026-00552-6

Figure Lengend Snippet: Scientific hypothesis. Deficiency of Drp1 in cerebellar PCs disrupts mitochondrial OXPHOS (including complexes III, IV, and V) and destabilizes the mitochondrial membrane. Reduced Coa6 expression further exacerbates complex IV impairment. These mitochondrial impairments culminate in a reduction of PC numbers, morphological abnormalities, and working memory deficits in mice. CoQ10 directly binds to Coa6 and elevates its expression, restoring complexes III, IV and V and mitochondrial membrane stability. Consequently, CoQ10 rescues the loss of dendritic spines in PCs and ameliorates working memory deficits in mice

Article Snippet: CoQ10 (HY-N0111, MCE, NJ) was dissolved in a 3% DMSO solution at a concentration of 500 μM.

Techniques: Membrane, Expressing