Uncharacterized protein C17orf80 – a novel interactor of human mitochondrial nucleoids

Author:

Potter Alisa12ORCID,Hangas Anu3,Goffart Steffi3ORCID,Huynen Martijn A.4ORCID,Cabrera-Orefice Alfredo24ORCID,Spelbrink Johannes N.12ORCID

Affiliation:

1. 1 Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands

2. Radboud Center for Mitochondrial Medicine (RCMM), Radboud University Medical Center 2 , Nijmegen, 6525 GA , The Netherlands

3. 3 Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, 80101, Finland

4. 4 Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands

Abstract

ABSTRACT Molecular functions of many human proteins remain unstudied, despite the demonstrated association with diseases or pivotal molecular structures, such as mitochondrial DNA (mtDNA). This small genome is crucial for the proper functioning of mitochondria, the energy-converting organelles. In mammals, mtDNA is arranged into macromolecular complexes called nucleoids that serve as functional stations for its maintenance and expression. Here, we aimed to explore an uncharacterized protein C17orf80, which was previously detected close to the nucleoid components by proximity labelling mass spectrometry. To investigate the subcellular localization and function of C17orf80, we took advantage of immunofluorescence microscopy, interaction proteomics and several biochemical assays. We demonstrate that C17orf80 is a mitochondrial membrane-associated protein that interacts with nucleoids even when mtDNA replication is inhibited. In addition, we show that C17orf80 is not essential for mtDNA maintenance and mitochondrial gene expression in cultured human cells. These results provide a basis for uncovering the molecular function of C17orf80 and the nature of its association with nucleoids, possibly leading to new insights about mtDNA and its expression.

Funder

Horizon 2020 Framework Programme

Marie Sklodowska-Curie Actions

ZonMw

Academy of Finland

Radboud Universiteit

Publisher

The Company of Biologists

Subject

Cell Biology

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