Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome

Emperador, Sonia; Garrido-Pérez, Nuria; Amezcua-Gil, Javier; Gaudó, Paula; Sanz, Julio Alberto Andrés; Yubero, Dèlia; Fernández–Marmiesse, Ana; O’Callaghan, María del Mar; Ortigoza‐Escobar, Juan Darío; Iriondo, Martí; Ruiz‐Pesini, Eduardo; García‐Cazorla, Àngels; Gil-Campos, Mercedes; Artuch, Rafael; Montoya, Julio; Bayona‐Bafaluy, M. Pilar

doi:10.3389/fgene.2019.01300

Cited by 9 publications

(13 citation statements)

References 25 publications

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“…F-box and leucine-rich repeat protein 4 (Fbxl4) is an orphan F-box protein localized to mitochondria [ 113 ]. Mutations in Fbxl4 have been reported in patients with early-onset encephalomyopathic mitochondrial DNA depletion [ 114 , 115 , 116 ]. Clinical symptoms include impairment of fetal movements and severe hypotonia at birth [ 114 , 115 ].…”

Section: The Role Of Cullin-1 Based Crls In Cross-striated Musclesmentioning

confidence: 99%

“…Mutations in Fbxl4 have been reported in patients with early-onset encephalomyopathic mitochondrial DNA depletion [ 114 , 115 , 116 ]. Clinical symptoms include impairment of fetal movements and severe hypotonia at birth [ 114 , 115 ]. Analysis of muscle biopsies revealed a decrease in mitochondrial mass as well as hyper fragmentation, respiratory chain deficiency, and a loss of mitochondrial membrane potential [ 113 , 114 ].…”

Section: The Role Of Cullin-1 Based Crls In Cross-striated Musclesmentioning

confidence: 99%

“…Mutations in Fbxl4 have been reported in patients with early-onset encephalomyopathic mitochondrial DNA depletion [114][115][116]. Clinical symptoms include impairment of fetal movements and severe hypotonia at birth [114,115].…”

Section: Fbxl4mentioning

confidence: 99%

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The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease

Blondelle

Biju

Lange

2020

IJMS

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The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin–proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and crucial roles in cross striated muscles than previously anticipated. This review highlights some of the findings on the multifaceted functions of cullin-RING E3-ligases, their substrate adapters, muscle protein substrates, and regulatory proteins, such as the Cop9 signalosome, for the development of cross striated muscles, and their roles in the etiology of myopathies.

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Section: The Role Of Cullin-1 Based Crls In Cross-striated Musclesmentioning

confidence: 99%

Section: The Role Of Cullin-1 Based Crls In Cross-striated Musclesmentioning

confidence: 99%

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The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease

Blondelle

Biju

Lange

2020

IJMS

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“…Skeletal muscle commonly shows mitochondrial dysfunctions with combined deficiencies of multiple OXPHOS complexes and mtDNA depletion. Patient’s fibroblasts typically display fragmented mitochondria and combined deficiencies of multiple OXPHOS complexes [ 98 , 99 , 100 , 101 , 130 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 ].…”

Section: Mitochondrial Dynamics Related Disordersmentioning

confidence: 99%

Mitochondrial Dynamics: Molecular Mechanisms, Related Primary Mitochondrial Disorders and Therapeutic Approaches

Nottia

Verrigni

Torraco

et al. 2021

Genes

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Mitochondria do not exist as individual entities in the cell—conversely, they constitute an interconnected community governed by the constant and opposite process of fission and fusion. The mitochondrial fission leads to the formation of smaller mitochondria, promoting the biogenesis of new organelles. On the other hand, following the fusion process, mitochondria appear as longer and interconnected tubules, which enhance the communication with other organelles. Both fission and fusion are carried out by a small number of highly conserved guanosine triphosphatase proteins and their interactors. Disruption of this equilibrium has been associated with several pathological conditions, ranging from cancer to neurodegeneration, and mutations in genes involved in mitochondrial fission and fusion have been reported to be the cause of a subset of neurogenetic disorders.

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“…Mitochondrial diseases are rare conditions caused by dysfunction of the oxidative phosphorylation system. In cellular models of these pathologies, trans-mitochondrial cybrids and human skin-derived fibroblasts showed evidence of altered autophagic flux, accumulation of autophagy markers, and higher mitophagic activity [134][135][136][137][138][139]. In addition, deregulated autophagy has been described in animal models of mitochondrial diseases: (i) an autophagic starvation-like response and mitophagy in the skeletal muscle of a mouse model of mitochondrial myopathy [140,141], and (ii) increased autophagosome numbers in retinal ganglion cells of a murine model of dominant optic atrophy [142].…”

Section: Mitochondrial Diseasesmentioning

confidence: 99%

Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot

Humbert

Morán

Cruz‐Ojeda

et al. 2020

Biology

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Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples.

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Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome

Cited by 9 publications

References 25 publications

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease

Mitochondrial Dynamics: Molecular Mechanisms, Related Primary Mitochondrial Disorders and Therapeutic Approaches

Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot

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