Loss of C2 Domain Protein (C2CD5) Alters Hypothalamic Mitochondrial Trafficking, Structure, and Function

Chaitanya K. Gavini, Chelsea R. White, Virginie Mansuy-Aubert, Gregory Aubert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: Mitochondria are essential organelles required for several cellular processes ranging from ATP production to cell maintenance. To provide energy, mitochondria are transported to specific cellular areas in need. Mitochondria also need to be recycled. These mechanisms rely heavily on trafficking events. While mechanisms are still unclear, hypothalamic mitochondria are linked to obesity. Methods: We used C2 domain protein 5 (C2CD5, also called C2 domain-containing phosphoprotein [CDP138]) whole-body KO mice primary neuronal cultures and cell lines to perform electron microscopy, live cellular imaging, and oxygen consumption assay to better characterize mitochondrial alteration linked to C2CD5. Results: This study identified that C2CD5 is necessary for proper mitochondrial trafficking, structure, and function in the hypothalamic neurons. We previously reported that mice lacking C2CD5 were obese and displayed reduced functional G-coupled receptor, melanocortin receptor 4 (MC4R) at the surface of hypothalamic neurons. Our data suggest that in neurons, normal MC4R endocytosis/trafficking necessities functional mitochondria. Discussion: Our data show that C2CD5 is a new protein necessary for normal mitochondrial function in the hypothalamus. Its loss alters mitochondrial ultrastructure, localization, and activity within the hypothalamic neurons. C2CD5 may represent a new protein linking hypothalamic dysfunction, mitochondria, and obesity.

Original languageEnglish (US)
Pages (from-to)324-337
Number of pages14
JournalNeuroendocrinology
Volume112
Issue number4
DOIs
StatePublished - Mar 1 2022

Keywords

  • Food intake
  • Hypothalamus
  • Mitochondria

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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