2. Academic Validation
  3. Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

  • Cell Metab. 2020 May 5;31(5):987-1003.e8. doi: 10.1016/j.cmet.2020.04.007.
Stéphanie Herkenne 1,  Olivier Ek 2,  Margherita Zamberlan 1,  Anna Pellattiero 1,  Maya Chergova 1,  Iñigo Chivite 3,  Eliška Novotná 1,  Giovanni Rigoni 2,  Tiago Branco Fonseca 1,  Dijana Samardzic 1,  Andrielly Agnellini 4,  Camilla Bean 1,  Giulietta Di Benedetto 5,  Natascia Tiso 2,  Francesco Argenton 2,  Antonella Viola 4,  Maria Eugenia Soriano 2,  Marta Giacomello 6,  Elena Ziviani 2,  Gabriele Sales 2,  Marc Claret 3,  Mariona Graupera 7,  Luca Scorrano 8
Affiliations

Affiliations

  • 1 Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
  • 2 Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
  • 3 Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; School of Medicine, Universitat de Barcelona, Barcelona, Spain.
  • 4 Department of Biomedical Sciences, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
  • 5 Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Institute of Neuroscience, CNR, Padova, Italy.
  • 6 Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; Department of Biomedical Sciences, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
  • 7 Vascular Signalling Laboratory, ProCURE and Oncobell Programs, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, l'Hospitalet de Llobregat, Barcelona 08908, Spain; CIBERONC, Instituto de Salud Carlos III, Av. de Monforte de Lemos, 5, 28029 Madrid, Spain.
  • 8 Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy. Electronic address: luca.scorrano@unipd.it.
PMID: 32315597 DOI: 10.1016/j.cmet.2020.04.007
Abstract

While endothelial cell (EC) function is influenced by Mitochondrial Metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Our data identify Opa1 as a crucial component of physiological and tumor angiogenesis.

Keywords

NFκB; Opa1; angiogenesis; cancer; fusion-fission; lymphangiogenesis; metastasis; mitochondria; mouse; tumor; zebrafish.

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