Ian Holt
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View article: Aspartame decreases fat deposits in mice at a cost of mild cardiac hypertrophy and reduced cognitive performance
Aspartame decreases fat deposits in mice at a cost of mild cardiac hypertrophy and reduced cognitive performance Open
View article: Characterising PMP22-Proximal Partners in a Schwann Cell Model of Charcot–Marie–Tooth Disease Type1A
Characterising PMP22-Proximal Partners in a Schwann Cell Model of Charcot–Marie–Tooth Disease Type1A Open
Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary condition caused by the duplication of the PMP22 gene. Overexpression of peripheral myelin protein 22 in Schwann cells leads to myelin sheath defects and axonal loss. We have prod…
View article: Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis
Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis Open
View article: Deep learning-driven neuromorphogenesis screenings identify repurposable drugs for mitochondrial disease
Deep learning-driven neuromorphogenesis screenings identify repurposable drugs for mitochondrial disease Open
Summary Mitochondrial disease encompasses untreatable conditions affecting tissues with high energy demands. A severe manifestation of mitochondrial disease is Leigh syndrome (Leigh), which causes defects in basal ganglia and midbrain regi…
View article: Proteomic characterization of human LMNA-related congenital muscular dystrophy muscle cells
Proteomic characterization of human LMNA-related congenital muscular dystrophy muscle cells Open
LMNA-related congenital muscular dystrophy (L-CMD) is caused by mutations in the LMNA gene, encoding lamin A/C. To further understand the molecular mechanisms of L-CMD, proteomic profiling using DIA mass spectrometry was conducted on immor…
View article: Mitochondrial DNA competition: starving out the mutant genome
Mitochondrial DNA competition: starving out the mutant genome Open
High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation of such mutants may also contribute to common disorders. Thus, selecting against these mutants is a major goal in mitochondr…
View article: Energy scarcity and impaired mitochondrial translation induce perinuclear stress granule clustering
Energy scarcity and impaired mitochondrial translation induce perinuclear stress granule clustering Open
Many proteins linked to amyotrophic lateral sclerosis and fronto-temporal dementia (ALS-FTD) change their cellular location and coalesce in cytoplasmic inclusion bodies in the disease state; yet the factors that govern protein relocation a…
View article: Metabolic Malfunction Mars Muscle Mitochondria
Metabolic Malfunction Mars Muscle Mitochondria Open
View article: Lipid Dysregulation Unveil the Intricate Interplay of Lysosomal and Mitochondrial Changes in Frontotemporal Dementia with GRN Haploinsufficiency
Lipid Dysregulation Unveil the Intricate Interplay of Lysosomal and Mitochondrial Changes in Frontotemporal Dementia with GRN Haploinsufficiency Open
This study investigates the cellular pathology resulting from haploinsufficiency of progranulin (PGRN) in frontotemporal dementia (FTD) associated with granulin (GRN) mutations. Utilizing fibroblasts from FTD patients carrying a distinctiv…
View article: Elevated cholesterol in <i>ATAD3</i> mutants is a compensatory mechanism that leads to membrane cholesterol aggregation
Elevated cholesterol in <i>ATAD3</i> mutants is a compensatory mechanism that leads to membrane cholesterol aggregation Open
Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether t…
View article: The Proteome Signatures of Fibroblasts from Patients with Severe, Intermediate and Mild Spinal Muscular Atrophy Show Limited Overlap
The Proteome Signatures of Fibroblasts from Patients with Severe, Intermediate and Mild Spinal Muscular Atrophy Show Limited Overlap Open
Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) has focused on SMA I. Here, proteomic profiling of skin fibroblasts from severe (SMA I), intermediate (SMA II), and mild (SMA III) patients, alongsid…
View article: 2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart
2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart Open
View article: Defects of Nutrient Signaling and Autophagy in Neurodegeneration
Defects of Nutrient Signaling and Autophagy in Neurodegeneration Open
Graphical Abstract Schematic Representation Highlighting the Mechanisms of Nutrient Sensing and Autophagy Under Physiological Conditions.
View article: 2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA
2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA Open
View article: OTHER NMDs
OTHER NMDs Open
View article: An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs
An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs Open
View article: Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks
Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks Open
Analysis of human heart mitochondrial DNA (mtDNA) by electron microscopy and agarose gel electrophoresis revealed a complete absence of the θ-type replication intermediates seen abundantly in mtDNA from all other tissues. Instead only Y- a…
View article: Mammalian Mitochondrial DNA Replication Intermediates Are Essentially Duplex but Contain Extensive Tracts of RNA/DNA Hybrid
Mammalian Mitochondrial DNA Replication Intermediates Are Essentially Duplex but Contain Extensive Tracts of RNA/DNA Hybrid Open
We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mtDNA replication intermediates (mtRIs) are essentially duplex throughout their length, but contain ext…
View article: Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism
Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism Open
View article: Additional file 1 of An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs
Additional file 1 of An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs Open
Additional file 1. Table; Unfiltered mass spectrometry results.
View article: Nesprin-1-alpha2 associates with kinesin at myotube outer nuclear membranes, but is restricted to neuromuscular junction nuclei in adult muscle
Nesprin-1-alpha2 associates with kinesin at myotube outer nuclear membranes, but is restricted to neuromuscular junction nuclei in adult muscle Open
Nesprins, nuclear envelope spectrin-repeat proteins encoded by the SYNE1 and SYNE2 genes, are involved in localization of nuclei. The short isoform, nesprin-1-alpha2, is required for relocation of the microtubule organizer function from ce…
View article: Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy
Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy Open
Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defect…
View article: The mitochondrial R-loop
The mitochondrial R-loop Open
The DNA in mitochondria contributes essential components of the organelle's energy producing machinery that is essential for life. In 1971, many mitochondrial DNA molecules were found to have a third strand of DNA that maps to a region con…
View article: MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy
MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy Open
Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with impaire…
View article: Two alternatively-spliced human nebulin isoforms with either exon 143 or exon 144 and their developmental regulation
Two alternatively-spliced human nebulin isoforms with either exon 143 or exon 144 and their developmental regulation Open
View article: Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication
Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication Open
Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the factors th…
View article: <scp>LETM</scp> 1 couples mitochondrial <scp>DNA</scp> metabolism and nutrient preference
<span>LETM</span> 1 couples mitochondrial <span>DNA</span> metabolism and nutrient preference Open
View article: Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model
Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model Open
All DNA polymerases misincorporate ribonucleotides despite their preference for deoxyribonucleotides, and analysis of cultured cells indicates that mammalian mitochondrial DNA (mtDNA) tolerates such replication errors. However, it is not c…
View article: Reply: Genotype-phenotype correlation in ATAD3A deletions: not just of scientific relevance
Reply: Genotype-phenotype correlation in ATAD3A deletions: not just of scientific relevance Open
View article: Clinicopathologic and molecular spectrum of <i>RNASEH1</i> -related mitochondrial disease
Clinicopathologic and molecular spectrum of <i>RNASEH1</i> -related mitochondrial disease Open
In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analy…