scholarly journals Mutations in the Complex III Assembly Factor Tetratricopeptide 19 Gene TTC19 Are a Rare Cause of Leigh Syndrome

2013 ◽  
pp. 43-45 ◽  
Author(s):  
P. S. Atwal
Keyword(s):  
Leigh Syndrome ◽  
Complex Iii ◽  
Assembly Factor

Mutations in the complex III assembly factor tetratricopeptide 19 gene TTC19 are a rare cause of Leigh syndrome

Mitochondrion ◽  
2013 ◽  
Vol 13 (6) ◽  
pp. 938
Author(s):  
P.S. Atwal ◽  
S. Schelley ◽  
G.M. Enns
Keyword(s):  
Leigh Syndrome ◽  
Complex Iii ◽  
Assembly Factor

scholarly journals Preprotein Translocase of the Outer Mitochondrial Membrane: Molecular Dissection and Assembly of the General Import Pore Complex

1998 ◽  
Vol 18 (11) ◽  
pp. 6515-6524 ◽  
Author(s):  
Peter J. T. Dekker ◽  
Michael T. Ryan ◽  
Jan Brix ◽  
Hanne Müller ◽  
Angelika Hönlinger ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Complex Iii ◽  
Outer Mitochondrial Membrane ◽  
Molecular Architecture ◽  
Molecular Dissection ◽  
Yeast Mutant ◽  
Essential Proteins ◽  
Assembly Factor ◽  
Stable Association ◽  
Main Component

ABSTRACT The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). We have analyzed the molecular architecture of the Tom machinery. The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of ∼400,000 (∼400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. A yeast mutant lacking both Tom20 and Tom70 can still form the GIP complex when sufficient amounts of Tom22 are synthesized. Besides the essential proteins Tom22 and Tom40, the GIP complex contains three small subunits, Tom5, Tom6, and Tom7. In mutant mitochondria lacking Tom6, the interaction between Tom22 and Tom40 is destabilized, leading to the dissociation of Tom22 and the generation of a subcomplex of ∼100K containing Tom40, Tom7, and Tom5. Tom6 is required to promote but not to maintain a stable association between Tom22 and Tom40. The following conclusions are suggested. (i) The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. (ii) Tom20 and Tom70 are not essential for the generation of the GIP complex. (iii) Tom6 functions as an assembly factor for Tom22, promoting its stable association with Tom40.

scholarly journals Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

2021 ◽  
Author(s):  
Maxence Le Vasseur ◽  
Jonathan R. Friedman ◽  
Marco Jost ◽  
Jiawei Xu ◽  
Justin Yamada ◽  
...  
Keyword(s):  
Mitochondrial Diseases ◽  
Selective Inhibition ◽  
Proteolytic Processing ◽  
Complex Iii ◽  
Mitochondrial Complex ◽  
Inner Mitochondrial Membrane ◽  
Genome Wide ◽  
A Genome ◽  
Assembly Factor ◽  
Metabolic Conditions

AbstractDysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified OCIA domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. We find that OCIAD1 is an inner mitochondrial membrane protein that forms a complex with supramolecular prohibitin assemblies. Our data indicate that OCIAD1 is required for maintenance of normal steady state levels of Complex III and the proteolytic processing of the catalytic subunit cytochrome c1 (CYC1). In OCIAD1 depleted mitochondria, unprocessed CYC1 is hemylated and incorporated into Complex III. We propose that OCIAD1 acts as an adaptor within prohibitin assemblies to stabilize and/or chaperone CYC1 and to facilitate its proteolytic processing by the IMMP2L protease.

Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome

2017 ◽  
Vol 120 (3) ◽  
pp. 243-246 ◽  
Author(s):  
Fabian Baertling ◽  
Laura Sánchez-Caballero ◽  
Sharita Timal ◽  
Mariël AM van den Brand ◽  
Lock Hock Ngu ◽  
...  
Keyword(s):  
Complex I ◽  
Leigh Syndrome ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Assembly Factor ◽  
Complex I Assembly

A transcriptome screen in yeast identifies a novel assembly factor for the mitochondrial complex III

Mitochondrion ◽  
2011 ◽  
Vol 11 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Lise Mathieu ◽  
Sophie Marsy ◽  
Yann Saint-Georges ◽  
Claude Jacq ◽  
Geneviève Dujardin
Keyword(s):  
Complex Iii ◽  
Mitochondrial Complex ◽  
Assembly Factor

scholarly journals SURF1 mutations causative of Leigh syndrome impair human neurogenesis

2019 ◽  
Author(s):  
Gizem Inak ◽  
Agnieszka Rybak-Wolf ◽  
Pawel Lisowski ◽  
René Jüttner ◽  
Annika Zink ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Progenitor Cells ◽  
Leigh Syndrome ◽  
Mitochondrial Complex ◽  
Complex Iv ◽  
Disease Mechanisms ◽  
Assembly Factor ◽  
Potential Strategy ◽  
Induced Pluripotent

AbstractMutations in the mitochondrial complex IV assembly factor SURF1 represent a major cause of Leigh syndrome (LS), a rare fatal neurological disorder. SURF1-deficient animals have failed to recapitulate the neuronal pathology of human LS, hindering our understanding of the disease mechanisms. We generated induced pluripotent stem cells from LS patients carrying homozygous SURF1 mutations (SURF1 iPS) and performed biallelic correction via CRISPR/Cas9. In contrast to corrected cells, SURF1 iPS showed impaired neuronal differentiation. Aberrant bioenergetics in SURF1 iPS occurred already in neural progenitor cells (NPCs), disrupting their neurogenic potency. Cerebral organoids from SURF1 iPS were smaller and recapitulated the neurogenesis defects. Our data imply that SURF1 mutations cause a failure in the development of maturing neurons. Using NPC function as an interventional target, we identified SURF1 gene augmentation as a potential strategy for restoring neurogenesis in LS patients carrying SURF1 mutations.

scholarly journals Respiratory supercomplexes provide metabolic efficiency in zebrafish

2019 ◽  
Author(s):  
Carolina García-Poyatos ◽  
Sara Cogliati ◽  
Enrique Calvo ◽  
Pablo Hernansanz-Agustín ◽  
Sylviane Lagarrigue ◽  
...  
Keyword(s):  
Null Allele ◽  
Physiological Role ◽  
Complex Iii ◽  
Metabolic Efficiency ◽  
Metabolic Gene Expression ◽  
Oxphos System ◽  
Assembly Factor ◽  
Quaternary Structures ◽  
Expression Program

The oxidative phosphorylation (OXPHOS) system is a dynamic system in which the respiratory complexes coexist with super-assembled quaternary structures called supercomplexes (SCs). The physiological role of SCs is still disputed. Here we used zebrafish to study the relevance of respiratory SCs. We combined immunodetection analysis and deep data-independent proteomics to characterize these structures and found similar SCs to those described in mice, as well as novel SCs including III2+IV2, I+IV and I+III2+IV2. To study the physiological role of SCs, we generated two null allele zebrafish lines for supercomplex assembly factor 1 (SCAF1). SCAF1-/- fish displayed altered OXPHOS activity due to the disrupted interaction of complex III and IV. SCAF1-/- fish were smaller in size, and showed abnormal fat deposition and decreased female fertility. These physiological phenotypes were rescued by doubling the food supply, which correlated with improved bioenergetics and alterations in the metabolic gene expression program. These results reveal that SC assembly by SCAF1 modulates OXPHOS efficiency and allows for the optimization of metabolic resources.

scholarly journals Cryo-EM Structures of Respiratory bc1-cbb3 type CIII2CIV Supercomplex and Electronic Communication Between the Complexes

2020 ◽  
Author(s):  
Stefan Steimle ◽  
Trevor Van Eeuwen ◽  
Yavuz Ozturk ◽  
Hee Jong Kim ◽  
Merav Braitbard ◽  
...  
Keyword(s):  
Electron Transport ◽  
Structural Characteristics ◽  
Complex Iii ◽  
Gram Negative Bacteria ◽  
Transport Pathways ◽  
Gram Negative ◽  
Assembly Factor ◽  
Cyt C ◽  
Functional Relevance ◽  
Electron Transport Complexes

Abstract Respiratory electron transport complexes are organized as individual entities or combined as large super-complexes (SC). The Gram-negative bacteria deploy a mitochondrial-like cytochrome (cyt) bc1 (Complex III, CIII2), and may have specific cbb3-type cyt c oxidases (Complex IV, CIV) instead of the canonical aa3-type CIV. Electron transfer between these complexes is mediated by soluble (c2) and membrane-anchored (cy) cyts. Here, we report the first structure of a bc1-cbb3 type SC (CIII2CIV, 5.2Å resolution) and three conformers of native CIII2 (3.3Å resolution) of functional relevance. The SC contains all catalytic subunits and cofactors as well as two extra transmembrane helices attributed to cyt cy and the assembly factor CcoH. The cyt cy is integral to SC, its cyt domain is mobile and conveys electrons to CIV differently than cyt c2. For the first time, this work establishes the structural characteristics of membrane-confined and membrane-external electron transport pathways of SCs in Gram-negative bacteria.

A mouse model of the GRACILE mutation Bsc1l A232G — Clues for another complex III assembly factor during early ontogenesis

Mitochondrion ◽  
2011 ◽  
Vol 11 (4) ◽  
pp. 655
Author(s):  
Heike Kotarsky⁎ ◽  
Per Levéen ◽  
Eva Hanson ◽  
Vineta Fellman
Keyword(s):  
Mouse Model ◽  
Early Ontogenesis ◽  
Complex Iii ◽  
Assembly Factor

scholarly journals 1036 Gracile Syndrome in a Turkish Newborn Infant Caused by a Homozygous Mutation (P99L) in Complex Iii Assembly Factor BCS1L

2012 ◽  
Vol 97 (Suppl 2) ◽  
pp. A297-A297
Author(s):  
E. Serdaroglu ◽  
S. Takci ◽  
H. Kotarsky ◽  
O. Cil ◽  
E. Utine ◽  
...  
Keyword(s):  
Newborn Infant ◽  
Complex Iii ◽  
Homozygous Mutation ◽  
Assembly Factor
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