Nicotinamide riboside (NR) induces mitochondrial biogenesis and effectively ameliorates morphological and genetic landmarks of mitochondrial myopathy ASkeletal.

Slides:

Advertisements

Similar presentations

Volume 15, Issue 1, Pages (January 2012)

Advertisements

Hyp mice show hypertension and increased NCC expression and phosphorylation A–ESerum intact Fgf23 concentration (A, n = 8–9, Student's t‐test, *P =

Figure 1. Persistent expression of Cisd2 promotes longevity in mice

FIGURE 1: Plasma levels of indoxyl sulfate (IS) in four groups: Sham, Sham + AST-120, CKD and CKD + AST-120 mice (n = 12 for each group). Data are expressed.

GFP‐Sed5p localization defect in sgt2Δ.

Morphology of white adipose tissue and muscle in S1/3 KO mice of different ages Morphology of white adipose tissue and muscle in S1/3 KO mice of different.

Loss of Hdac3 impairs Ar signaling in mouse prostate tissues and has no effect on apoptosis Loss of Hdac3 impairs Ar signaling in mouse prostate tissues.

Tamoxifen induced deletion of FAK

Volume 26, Issue 2, Pages e5 (August 2017)

Volume 19, Issue 6, Pages (June 2014)

H3K9me2 and G9a levels decrease during adipogenesis.

Volume 85, Issue 6, Pages (June 2014)

Volume 21, Issue 11, Pages (November 2014)

PERK activator decreases pathological tau species in vivo

Neuro‐inflammatory cytokines, brain microglial activation, and working memory deficits are normalized using LV.IDS.ApoEII, but not LV.IDS in MPS II mice.

Volume 25, Issue 2, Pages (February 2017)

Effects on the content of mtDNA and the expression of the OXPHOS genes by deletion of SHMT2 in 293A cells. Effects on the content of mtDNA and the expression.

[68Ga]Pentixafor PET imaging of MM xenografts Real‐time PCR analysis of cxcr4 transcript expression levels in HeLa (negative control) and in MM cell lines.

Volume 16, Issue 1, Pages 1-8 (June 2016)

TFE3 regulates glucose homeostasis

Differential accumulation of substrates in vivo

Metabolic profile of Tfe3 KO mice

Validation cell‐type‐enriched culturing methods, metabolome dynamics, and mitochondria abundance and bioenergetics in differentiating organoids Validation.

HSV‐1 depletes mt DNA and mt mRNA in infected Vero cells.

Mitochondrial HMGB1 is linked to mitochondrial functions Western blot with separated cellular components from the cerebellar tissues of the three genotypes.

Identification of miR‐499 targets

Effect of HUWE1 on MYC and MIZ1 complexes Immunoblot documenting levels of MYC and MIZ1 upon HUWE1 overexpression. Effect of HUWE1 on MYC and MIZ1 complexes.

Combination of OTX‐015 and PD does not induce overt toxicity

Fig. 1. Muscles of LAMA2 MD patients and dyW/dyW mice contain high amounts of laminin-α4 and show deficits in BM. Muscles of LAMA2 MD patients and dyW/dyW.

Volume 15, Issue 1, Pages (January 2012)

Neuro‐inflammatory cytokines, brain microglial activation, and working memory deficits are normalized using LV.IDS.ApoEII, but not LV.IDS in MPS II mice.

Zc3h10 overexpression boosts mitochondrial function and density in myotubes Zc3h10 overexpression boosts mitochondrial function and density in myotubes.

Volume 22, Issue 1, Pages (January 2014)

Molecular and morphological analysis of Pitrm1+/− mouse brain

Volume 25, Issue 2, Pages (February 2017)

Nec‐1 inhibits the phosphorylation and aggregation of tau

Volume 26, Issue 2, Pages e5 (August 2017)

Hdac3 deletion decreases AKT phosphorylation and tumor growth in Pten knockout prostate cancer Hdac3 deletion decreases AKT phosphorylation and tumor growth.

Impaired ECM protein synthesis in infarcted area of S100a4cre+/− × Fstl1flox/flox mice Impaired ECM protein synthesis in infarcted area of S100a4cre+/−

Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy

Figure 1 The de novo p.Lys33Gln mutation leads to OXPHOS defect in muscle The de novo p.Lys33Gln mutation leads to OXPHOS defect in muscle (A) Histopathologic.

PERK activator decreases pathological tau species in vitro

A Heterozygous Truncating Mutation in RRM2B Causes Autosomal-Dominant Progressive External Ophthalmoplegia with Multiple mtDNA Deletions Henna Tyynismaa,

IL‐23‐induced psoriasis‐like skin disease is ameliorated in IL‐23−/− mice IL‐23‐induced psoriasis‐like skin disease is ameliorated in IL‐23−/− mice ARepresentative.

Figure 1 Oxidative phosphorylation

LV.IDS and LV.IDS.ApoEII improve brain‐specific IDS activity and express supra‐physiological levels of active IDS in peripheral organs LV.IDS and LV.IDS.ApoEII.

mGPDH is not essential to muscle development

PGC‐1α‐independent regulation of the slow‐twitch muscle fiber program by miR‐499 PGC‐1α‐independent regulation of the slow‐twitch muscle fiber program.

Volume 141, Issue 2, Pages (April 2010)

Association of total disease burden with age, m

Gain of FGF23 function induces renal Na+ retention through increased renal NCC expression and channel activation AUrine volume (n = 15–17), urinary Na+

An mtDNA Mutation in the Initiation Codon of the Cytochrome C Oxidase Subunit II Gene Results in Lower Levels of the Protein and a Mitochondrial Encephalomyopathy

EGFL7 increased surface expression of integrins α5β1 and αVβ3

C266S laforin's effect on LD‐associated general defect in autophagy

Volume 21, Issue 6, Pages (June 2015)

Volume 25, Issue 4, Pages e4 (April 2017)

Volume 10, Issue 2, Pages (August 2009)

Figure 3 In silico modelling of the human mt-AlaRS Arg580 residue and p.Arg580Trp variant. (A) Multiple sequence ... Figure 3 In silico modelling of the.

ZBTB48 is required for MTFP1 expression

Rescue of motor neurons from death The ventral root of the fifth lumbar segment (L5). Rescue of motor neurons from death The ventral root of the fifth.

The relationship between the genes in mice and human samples

MiR‐499 is dynamically regulated during muscle fiber type transition and affects mitochondrial function miR‐499 is dynamically regulated during muscle.

Figure 2 Analysis of muscle and nerve histopathology and muscle mtDNA deletions (A) Representative muscle biopsy shows a cytochrome c oxidase (COX)-negative.

Supraphysiological levels of GDF11 cause atrophy of striated muscle in vivo Supraphysiological levels of GDF11 cause atrophy of striated muscle in vivo.

Decreased brown adipose tissue (BAT) function in Deletors and the effects of nicotinamide riboside treatment for whole‐body metabolism, BAT, and liver.

Absence of miR‐21 in macrophages promotes foam cell formation

Disturbance of mTOR signaling in vivo in GAA‐KO mice

Volume 20, Issue 6, Pages (December 2014)

Why Have Organelles Retained Genomes?

Ju Youn Beak et al. BTS 2017;2:39-53

Presentation transcript:

Nicotinamide riboside (NR) induces mitochondrial biogenesis and effectively ameliorates morphological and genetic landmarks of mitochondrial myopathy ASkeletal muscle NAD+ content in 23‐ to 27‐month‐old Deletors and WT mice (n = 5 in each group). Nicotinamide riboside (NR) induces mitochondrial biogenesis and effectively ameliorates morphological and genetic landmarks of mitochondrial myopathy ASkeletal muscle NAD+ content in 23‐ to 27‐month‐old Deletors and WT mice (n = 5 in each group). BQuantification of muscle fibers showing decreased COX activity in histochemical analysis of frozen sections of quadriceps femoris muscle (total fibers n = 2000 counted per mouse); diet started before disease manifestation (pre‐manifestation, “pre”; Deletor NR n = 5; Deletor CD n = 4); diet started after disease manifestation (post‐manifestation, “post”; Deletor NR n = 12; CD n = 11). CQuantification of the overall histochemical COX activity in muscle. Total intensity of activity in the quadriceps femoris muscle measured (n = 6 in each group). DMitochondrial respiratory complex protein and ATPase protein amounts in quadriceps femoris muscle. Western blot analysis of post‐manifestation NR‐ and CD‐fed mouse groups. Representative results shown. CI, respiratory chain complex I, 39‐kDa subunit; CII, complex II, 70‐kDa subunit; CIV, complex IV, cytochrome c oxidase, COI subunit, 40 kDa; CV, complex V, ATPase, alpha subunit, 55 kDa. Tubulin indicates the loading control. E–HQuantification of the respiratory chain complex amounts from Western blots (Fig 1D). (Deletor NR n = 8; Deletor CD n = 8, WT NR n = 6, WT CD n = 6). IMultiple mtDNA deletions in quadriceps femoris muscle. Long‐range PCR amplification. 16.6 kb: amplification product from full‐length mtDNA; bracket: smear representing deleted mtDNA species; 549 bp, product from 12S rRNA gene in mtDNA, not carrying deletions and representing total mtDNA. Representative image (pre‐treatment Deletor NR n = 5; Deletor CD n = 4; post‐manifestation Deletor NR n = 12; Deletor CD n = 11). JQuantification of mtDNA deletion load (H). Pre‐ and post‐manifestation NR‐ and CD (pre‐manifestation; Deletor NR n = 5; Deletor CD n = 4), (post‐manifestation; Deletor NR n = 12; CD n = 11). KmtDNA copy number in quadriceps femoris muscle. Quantitative PCR analysis, using beta‐actin gene as a nuclear two‐copy control gene (post‐manifestation Deletor NR n = 12; Deletor CD n = 11, WT NR n = 8, WT CD n = 7). LCitrate synthase (CS) activity in quadriceps femoris muscle (n = 5 in each group). Numbers above columns indicate P‐values. All values are presented as mean ± s.e.m. (Student's t‐test). NR, nicotinamide riboside; CD, chow diet; Del, Deletor; WT, wild‐type mice; pre, pre‐manifestation age group; post, post‐manifestation age group; COX, cytochrome c oxidase; CI‐CIV respiratory chain complexes I‐IV; CV, ATP synthase; AU, arbitrary units.Source data are available for this figure. Nahid A Khan et al. EMBO Mol Med. 2014;6:721-731 © as stated in the article, figure or figure legend