Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice.
The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed.
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.|Hypertension, lipids and cardiovascular risk Group, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.|Integrin Signaling Laboratory, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Aleix
A
Sala-Vila
Integrin Signaling Laboratory, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Inmaculada
I
Navarro-Lérida
Integrin Signaling Laboratory, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Miguel
M
Sánchez-Alvarez
Cell Compartments and Signaling Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Marta
M
Bosch
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.|Hypertension, lipids and cardiovascular risk Group, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.
Carlos
C
Calvo
Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Juan Antonio
JA
López
Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Enrique
E
Calvo
The Institute for Molecular Bioscience; Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, Queensland, Australia.
Charles
C
Ferguson
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.|Department of Biology, University of Padova, Padova, Italy.
Marta
M
Giacomello
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.|Department of Biology, University of Padova, Padova, Italy.
Annalisa
A
Serafini
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.|Department of Biology, University of Padova, Padova, Italy.
Luca
L
Scorrano
Functional Genetics of the Oxidative Phosphorylation System, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
José Antonio
JA
Enriquez
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, Valladolid, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain.
Jesús
J
Balsinde
The Institute for Molecular Bioscience; Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, Queensland, Australia.
Robert G
RG
Parton
Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Jesús
J
Vázquez
Cell Compartments and Signaling Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Albert
A
Pol
Integrin Signaling Laboratory, Cell &Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Miguel A
MA
Del Pozo
D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D002458:Cell Fractionation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D020543:Proteome / Q000032:analysis
D051242:Caveolin 1; D020543:Proteome