Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects

Nikola Kovářová, Petr Pecina, Hana Nůsková, Marek Vrbacký, Massimo Zeviani, Tomáš Mráček, Carlo Viscomi, Josef Houštěk

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1-/- knockout leads only to a mild COX defect. We used SURF1-/- mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1-/- mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling.The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I-III2-IVn SCs in SURF1 patient fibroblasts, whereas SURF1-/- mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1-/- mouse liver and brain. Both the control and SURF1-/- mice revealed only negligible formation of the I-III2-IVn SCs and marked tissue differences in the contents of COX dimer and III2-IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I-III2-IVn supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.

Original languageEnglish
Pages (from-to)705-715
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1862
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Electron Transport Complex IV
Oxidoreductases
Fibroblasts
Leigh Disease
Liver
Mitochondrial Proteins
Brain
Knockout Mice
Electrophoresis
Myocardium

Keywords

  • Cytochrome c oxidase
  • Doxycycline
  • Leigh syndrome
  • Pulse-chase
  • Respiratory supercomplexes
  • SURF1 mouse knockout

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects. / Kovářová, Nikola; Pecina, Petr; Nůsková, Hana; Vrbacký, Marek; Zeviani, Massimo; Mráček, Tomáš; Viscomi, Carlo; Houštěk, Josef.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1862, No. 4, 01.04.2016, p. 705-715.

Research output: Contribution to journalArticle

Kovářová, N, Pecina, P, Nůsková, H, Vrbacký, M, Zeviani, M, Mráček, T, Viscomi, C & Houštěk, J 2016, 'Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1862, no. 4, pp. 705-715. https://doi.org/10.1016/j.bbadis.2016.01.007
Kovářová, Nikola ; Pecina, Petr ; Nůsková, Hana ; Vrbacký, Marek ; Zeviani, Massimo ; Mráček, Tomáš ; Viscomi, Carlo ; Houštěk, Josef. / Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2016 ; Vol. 1862, No. 4. pp. 705-715.
@article{44962a97e3a14e4d8f0b2c1b5227b279,
title = "Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects",
abstract = "Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1-/- knockout leads only to a mild COX defect. We used SURF1-/- mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1-/- mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling.The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I-III2-IVn SCs in SURF1 patient fibroblasts, whereas SURF1-/- mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1-/- mouse liver and brain. Both the control and SURF1-/- mice revealed only negligible formation of the I-III2-IVn SCs and marked tissue differences in the contents of COX dimer and III2-IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I-III2-IVn supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.",
keywords = "Cytochrome c oxidase, Doxycycline, Leigh syndrome, Pulse-chase, Respiratory supercomplexes, SURF1 mouse knockout",
author = "Nikola Kov{\'a}řov{\'a} and Petr Pecina and Hana Nůskov{\'a} and Marek Vrback{\'y} and Massimo Zeviani and Tom{\'a}š Mr{\'a}ček and Carlo Viscomi and Josef Houštěk",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.bbadis.2016.01.007",
language = "English",
volume = "1862",
pages = "705--715",
journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects

AU - Kovářová, Nikola

AU - Pecina, Petr

AU - Nůsková, Hana

AU - Vrbacký, Marek

AU - Zeviani, Massimo

AU - Mráček, Tomáš

AU - Viscomi, Carlo

AU - Houštěk, Josef

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1-/- knockout leads only to a mild COX defect. We used SURF1-/- mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1-/- mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling.The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I-III2-IVn SCs in SURF1 patient fibroblasts, whereas SURF1-/- mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1-/- mouse liver and brain. Both the control and SURF1-/- mice revealed only negligible formation of the I-III2-IVn SCs and marked tissue differences in the contents of COX dimer and III2-IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I-III2-IVn supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.

AB - Mitochondrial protein SURF1 is a specific assembly factor of cytochrome c oxidase (COX), but its function is poorly understood. SURF1 gene mutations cause a severe COX deficiency manifesting as the Leigh syndrome in humans, whereas in mice SURF1-/- knockout leads only to a mild COX defect. We used SURF1-/- mouse model for detailed analysis of disturbed COX assembly and COX ability to incorporate into respiratory supercomplexes (SCs) in different tissues and fibroblasts. Furthermore, we compared fibroblasts from SURF1-/- mouse and SURF1 patients to reveal interspecies differences in kinetics of COX biogenesis using 2D electrophoresis, immunodetection, arrest of mitochondrial proteosynthesis and pulse-chase metabolic labeling.The crucial differences observed are an accumulation of abundant COX1 assembly intermediates, low content of COX monomer and preferential recruitment of COX into I-III2-IVn SCs in SURF1 patient fibroblasts, whereas SURF1-/- mouse fibroblasts were characterized by low content of COX1 assembly intermediates and milder decrease in COX monomer, which appeared more stable. This pattern was even less pronounced in SURF1-/- mouse liver and brain. Both the control and SURF1-/- mice revealed only negligible formation of the I-III2-IVn SCs and marked tissue differences in the contents of COX dimer and III2-IV SCs, also less noticeable in liver and brain than in heart and muscle. Our studies support the view that COX assembly is much more dependent on SURF1 in humans than in mice. We also demonstrate markedly lower ability of mouse COX to form I-III2-IVn supercomplexes, pointing to tissue-specific and species-specific differences in COX biogenesis.

KW - Cytochrome c oxidase

KW - Doxycycline

KW - Leigh syndrome

KW - Pulse-chase

KW - Respiratory supercomplexes

KW - SURF1 mouse knockout

UR - http://www.scopus.com/inward/record.url?scp=84958212760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958212760&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2016.01.007

DO - 10.1016/j.bbadis.2016.01.007

M3 - Article

AN - SCOPUS:84958212760

VL - 1862

SP - 705

EP - 715

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 4

ER -