Cytochrome c oxidase deficiency

Brischigliaro, Michele; Zeviani, Massimo

doi:10.1016/j.bbabio.2020.148335

Cited by 72 publications

(70 citation statements)

References 248 publications

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“…Constitutive knockouts of single-isoform subunits or assembly factors of CIV generally lead to embryonic lethality, and therefore, most viable CIV deficiency models carry conditional knockout alleles. A recent review exhaustively covers CIV deficiencies in humans and model organisms [80]. The outcome of both CIII and CIV deficiencies, in theory, should be compromised CoQ oxidation, but how the blockade of these two different sites of ETS differ respective to CoQ pool redox status, ROS production, OXPHOS efficiency, and mitochondrial membrane potential remains poorly understood.…”

Section: Mouse Models With Coq-ciii-civ Segment Dysfunctionmentioning

confidence: 99%

The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology

2021

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depends on CoQ reoxidation by the mitochondrial complex III (cytochrome bc 1 complex, CIII). However, the literature is surprisingly limited as for the role of the CoQ-linked metabolism in the pathogenesis of human diseases of oxidative phosphorylation (OXPHOS), in which the CoQ homeostasis is directly or indirectly affected. In this review, we give an introduction to CIII function, and an overview of the pathological consequences of CIII dysfunction in humans and mice and of the CoQ-dependent metabolic processes potentially affected in these pathological states. Finally, we discuss some experimental tools to dissect the various aspects of compromised CoQ oxidation.

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Section: Mouse Models With Coq-ciii-civ Segment Dysfunctionmentioning

confidence: 99%

The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology

2021

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“…COX1 is the mitochondrial-encoded headstone subunit of cytochrome c oxidase (complex IV). Loss of COX1 leads to complex IV deficiency, as apparent in several mitochondrial disorder patients (Brischigliaro and Zeviani, 2021;Fontanesi and Barrientos, 2013;Shoubridge, 2001;Weraarpachai et al, 2009Weraarpachai et al, , 2012. OXA1L inserts COX1 co-translationally into the membrane.…”

Section: Dissecting Early Steps Of Cox1 Biogenesismentioning

confidence: 99%

“…Considering the importance of OXPHOS for cellular function, it is not surprising that defects at every step of the mitochondrial gene expression process have been linked to human disorders (Brischigliaro and Zeviani, 2021;Fontanesi and Barrientos, 2013). Most of the patients display neuromuscular pathologies, which have been attributed to the especially high energy (A) Jac1 (coupled to DyLight488) was imported into isolated HEK293T mitochondria and treated or not with proteinase K. Dc, membrane potential.…”

Section: Introductionmentioning

confidence: 99%

An in vitro system to silence mitochondrial gene expression

Cruz-Zaragoza,

Dennerlein,

Linden

et al. 2021

Cell

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“…Interestingly, Cox12 is probably not essential for CcO activity per se since detergentpurified CcO remained active despite the loss of Cox12 during the purification 7 . Yeast Cox12p is the ortholog of human COX6B and two missense mutations in the COX6B1 isoform caused severe clinical symptoms 8 , supporting the functional importance of the protein. The precise function of Cox12 is currently unknown but Ghosh et al suggested a link with the copper delivery pathway to Cox2 9 .…”

Section: Introductionmentioning

confidence: 93%

The [PSI+] prion and HSP104 modulate cytochromecoxidase deficiency caused by deletion of COX12

Saini

Dawitz

Aufschnaiter

et al. 2021

Preprint

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Cytochrome c oxidase is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of cytochrome c oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here, experimental evolution of a Saccharomyces cerevisiae Δcox12 strain for ≈300 generations allowed to restore the activity of cytochrome c oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the AAA+ disaggregase Hsp104. Deletion or overexpression of Hsp104 also increased respiration of the Δcox12 ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [PSI+] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.

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Cytochrome c oxidase deficiency

Cited by 72 publications

References 248 publications

The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology

The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology

An in vitro system to silence mitochondrial gene expression

The [PSI+] prion and HSP104 modulate cytochromecoxidase deficiency caused by deletion of COX12

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