Mitochondrial disorders of the OXPHOS system

Fernández-Vizarra, Erika; Zeviani, Massimo

doi:10.1002/1873-3468.13995

Cited by 168 publications

(141 citation statements)

References 536 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…The development of next generation sequencing has led to a significant improvement in the genetic diagnostic capacity in the last ten years, dramatically expanding the scenario of the genetic basis of mitochondrial diseases [ 69 ]. The diagnostic power may improve with “multi-omics” integrative approaches too [ 70 ].…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Syndromes Revisited

Orsucci¹,

Ienco²,

Rossi³

et al. 2021

JCM

View full text Add to dashboard Cite

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

show abstract

Section: Resultsmentioning

confidence: 99%

Mitochondrial Syndromes Revisited

Orsucci¹,

Ienco²,

Rossi³

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…Mitochondrial diseases are generally provoked by genetic mutations in complexes’ subunits or assembly factors, as extensively discussed in numerous other reviews [ 276 , 277 , 278 , 279 , 280 ]. However, defects in the machinery involved in the import of these subunits have also been identified as the cause of mitochondrial pathologies, leading to different clinical features.…”

Section: Pathologies With Underlying Mitochondrial Import Defectsmentioning

confidence: 99%

Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Needs

Protasoni

Henley

et al. 2021

Life

View full text Add to dashboard Cite

The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease.

show abstract

“…Accordingly, the clinical phenotype and the severity of biochemical dysfunctions are highly variable, and pathology only manifests when the percentage of mutated mtDNA exceeds a threshold, which is variable for each kind of mutation. For a recent exhaustive review on the genetic basis of primary mitochondrial diseases we refer to Fernandez-Vizarra and Zeviani, 2020 [26].…”

Section: Both Genomes Contribute To the Onset Of Mitochondrial Diseasesmentioning

confidence: 99%

Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences

Rugolo

Zanna

Ghelli

2021

Life

View full text Add to dashboard Cite

The mitochondrial respiratory chain encompasses four oligomeric enzymatic complexes (complex I, II, III and IV) which, together with the redox carrier ubiquinone and cytochrome c, catalyze electron transport coupled to proton extrusion from the inner membrane. The protonmotive force is utilized by complex V for ATP synthesis in the process of oxidative phosphorylation. Respiratory complexes are known to coexist in the membrane as single functional entities and as supramolecular aggregates or supercomplexes (SCs). Understanding the assembly features of SCs has relevant biomedical implications because defects in a single protein can derange the overall SC organization and compromise the energetic function, causing severe mitochondrial disorders. Here we describe in detail the main types of SCs, all characterized by the presence of complex III. We show that the genetic alterations that hinder the assembly of Complex III, not just the activity, cause a rearrangement of the architecture of the SC that can help to preserve a minimal energetic function. Finally, the major metabolic disturbances associated with severe SCs perturbation due to defective complex III are discussed along with interventions that may circumvent these deficiencies.

show abstract

Mitochondrial disorders of the OXPHOS system

Cited by 168 publications

References 536 publications

Mitochondrial Syndromes Revisited

Mitochondrial Syndromes Revisited

Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences

Contact Info

Product

Resources

About