Difference between revisions of "Lobo-Jarne 2018 Cell Rep"
(Created page with "{{Publication |title=Lobo-Jarne T, Nývltová E, Pérez-Pérez R, Timón-Gómez A, Molinié T, Choi A, Mourier A, Fontanesi F, Ugalde C, Barrientos A (2018) Human COX7A2L regu...") |
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|journal=Cell Rep | |journal=Cell Rep | ||
|abstract=The mitochondrial respiratory chain is organized in a dynamic set of supercomplexes (SCs). The COX7A2L protein is essential for mammalian SC III<sub>2</sub>+IV assembly. However, its function in respirasome (SCs I+III<sub>2</sub>+IV<sub>n</sub>) biogenesis remains controversial. To unambiguously determine the COX7A2L role, we generated COX7A2L-knockout (COX7A2L-KO) HEK293T and U87 cells. COX7A2L-KO cells lack SC III<sub>2</sub>+IV but have enhanced complex III steady-state levels, activity, and assembly rate, normal ''de novo'' complex IV biogenesis, and delayed respirasome formation. Nonetheless, the KOs have normal respirasome steady-state levels, and only larger structures (SCs I<sub>1-2</sub>+III<sub>2</sub>+IV<sub>2-n</sub> or megacomplexes) were undetected. Functional substrate-driven competition assays showed normal mitochondrial respiration in COX7A2L-KO cells in standard and nutritional-, environmental-, and oxidative-stress-challenging conditions. We conclude that COX7A2L establishes a regulatory checkpoint for the biogenesis of CIII<sub>2</sub> and specific SCs, but the COX7A2L-dependent MRC remodeling is essential neither to maintain mitochondrial bioenergetics nor to cope with acute cellular stresses. | |abstract=The mitochondrial respiratory chain is organized in a dynamic set of supercomplexes (SCs). The COX7A2L protein is essential for mammalian SC III<sub>2</sub>+IV assembly. However, its function in respirasome (SCs I+III<sub>2</sub>+IV<sub>n</sub>) biogenesis remains controversial. To unambiguously determine the COX7A2L role, we generated COX7A2L-knockout (COX7A2L-KO) HEK293T and U87 cells. COX7A2L-KO cells lack SC III<sub>2</sub>+IV but have enhanced complex III steady-state levels, activity, and assembly rate, normal ''de novo'' complex IV biogenesis, and delayed respirasome formation. Nonetheless, the KOs have normal respirasome steady-state levels, and only larger structures (SCs I<sub>1-2</sub>+III<sub>2</sub>+IV<sub>2-n</sub> or megacomplexes) were undetected. Functional substrate-driven competition assays showed normal mitochondrial respiration in COX7A2L-KO cells in standard and nutritional-, environmental-, and oxidative-stress-challenging conditions. We conclude that COX7A2L establishes a regulatory checkpoint for the biogenesis of CIII<sub>2</sub> and specific SCs, but the COX7A2L-dependent MRC remodeling is essential neither to maintain mitochondrial bioenergetics nor to cope with acute cellular stresses. | ||
|keywords=COX7A2L, COX7RP, SCAFI, Complex III, Mitochondrial respiratory chain, Respirasomes, Supercomplexes | |keywords=COX7A2L, COX7RP, SCAFI, Complex III, Mitochondrial respiratory chain, Respirasomes, Supercomplexes, Human glioblastoma U87 cells | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=US FL Miami Moraes CT | |mipnetlab=US FL Miami Moraes CT | ||
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|area=Respiration, Genetic knockout;overexpression | |area=Respiration, Genetic knockout;overexpression | ||
|organism=Human | |organism=Human | ||
|tissues=HEK | |tissues=Other cell lines, HEK | ||
|preparations=Permeabilized cells | |preparations=Permeabilized cells | ||
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex | |enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex | ||
|couplingstates=LEAK, OXPHOS, ET | |couplingstates=LEAK, OXPHOS, ET | ||
|pathways=N, S, NS, ROX | |pathways=N, S, Gp, NS, ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2018-12, | ||
}} | }} |
Revision as of 11:06, 25 July 2019
Lobo-Jarne T, Nývltová E, Pérez-Pérez R, Timón-Gómez A, Molinié T, Choi A, Mourier A, Fontanesi F, Ugalde C, Barrientos A (2018) Human COX7A2L regulates complex III biogenesis and promotes supercomplex organization remodeling without affecting mitochondrial bioenergetics. Cell Rep 25:1786-99. |
Lobo-Jarne T, Nyvltova E, Perez-Perez R, Timon-Gomez A, Molinie T, Choi A, Mourier A, Fontanesi F, Ugalde C, Barrientos A (2018) Cell Rep
Abstract: The mitochondrial respiratory chain is organized in a dynamic set of supercomplexes (SCs). The COX7A2L protein is essential for mammalian SC III2+IV assembly. However, its function in respirasome (SCs I+III2+IVn) biogenesis remains controversial. To unambiguously determine the COX7A2L role, we generated COX7A2L-knockout (COX7A2L-KO) HEK293T and U87 cells. COX7A2L-KO cells lack SC III2+IV but have enhanced complex III steady-state levels, activity, and assembly rate, normal de novo complex IV biogenesis, and delayed respirasome formation. Nonetheless, the KOs have normal respirasome steady-state levels, and only larger structures (SCs I1-2+III2+IV2-n or megacomplexes) were undetected. Functional substrate-driven competition assays showed normal mitochondrial respiration in COX7A2L-KO cells in standard and nutritional-, environmental-, and oxidative-stress-challenging conditions. We conclude that COX7A2L establishes a regulatory checkpoint for the biogenesis of CIII2 and specific SCs, but the COX7A2L-dependent MRC remodeling is essential neither to maintain mitochondrial bioenergetics nor to cope with acute cellular stresses. • Keywords: COX7A2L, COX7RP, SCAFI, Complex III, Mitochondrial respiratory chain, Respirasomes, Supercomplexes, Human glioblastoma U87 cells • Bioblast editor: Plangger M • O2k-Network Lab: US FL Miami Moraes CT
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Human
Tissue;cell: Other cell lines, HEK
Preparation: Permeabilized cells
Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, Gp, NS, ROX HRR: Oxygraph-2k
2018-12