Human NME6 protein: subcellular localization, structure and function

Proust, Bastien (2022) Human NME6 protein: subcellular localization, structure and function. Doctoral thesis, Sveučilište u Zagrebu, Prirodoslovno-Matematički Fakultet.

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Abstract

Nucleoside diphosphate kinase (NDPK/NME/NM23) family of enzymes catalyze the transfer of gamma phosphate group from nucleoside triphosphates to nucleoside diphosphates. The family sparked interest after the discovery of metastasis suppressor activity of NME1, leading to a comprehensive characterization of Group I members (NME1-NME4). In contrast, the evolutionary ancient Group II members (NME5-NME9) are to date barely explored. We aimed to produce an extensive description of the human NME6 protein, by revealing its expression pattern, enzymatic activity, subcellular localization, quaternary structure and cellular function. Our results show the ubiquitous expression of NME6. We demonstrated a lack of enzymatic activity linked to oligomerization deficiency. We confirmed the mitochondrial localization and refined it to a matrix-facing protein, partially bound to the mitochondrial inner membrane, where NME6 interacts with RCC1L protein. Finally, we unraveled a negative impact of NME6 on mitochondrial respiration, possibly linked to the regulation of mitochondria-encoded protein expression.

Item Type:

Thesis (Doctoral thesis)

Uncontrolled Keywords:

NME ; NM23 ; NDPK ; NME6 ; RCC1L ; WBSCR16 ; Mitochondria

Subjects:

NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology

Divisions:

Division of Molecular Biology

Projects: