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Obesity is a public health crisis, and its prevalence disproportionately affects African Americans in the United States. Dysregulation of organelle calcium homeostasis is associated with obesity. The mitochondrial calcium uniporter (MCU) complex is primarily responsible for mitochondrial calcium homeostasis. Obesity is a multifactorial disease in which genetic underpinnings such as single-nucleotide polymorphisms (SNPs) may contribute to disease progression. The objective of this study was to identify genetic variations of MCU with anthropometric measurements and obesity in the All of Us Research Program. Methods: We used an additive genetic model to assess the association between obesity traits (body mass index (BMI), waist and hip circumference) and selected MCU SNPs in 19,325 participants (3221 normal weight and 16,104 obese). Eleven common MCU SNPs with a minor allele frequency ≥ 5% were used for analysis. Results: We observed three MCU SNPs in self-reported Black/African American (B/AA) men, and six MCU SNPs in B/AA women associated with increased risk of obesity, whereas six MCU SNPs in White men, and nine MCU SNPs in White women were protective against obesity development. Conclusions: This study found associations of MCU SNPs with obesity, providing evidence of a potential predictor of obesity susceptibility in B/AA adults. 

Mitochondria contain connexins, a family of proteins that is known to form gap junction channels. Connexins are synthesized in the endoplasmic reticulum and oligomerized in the Golgi to form hemichannels. Hemichannels from adjacent cells dock with one another to form gap junction channels that aggregate into plaques and allow cell–cell communication. Cell–cell communication was once thought to be the only function of connexins and their gap junction channels. In the mitochondria, however, connexins have been identified as monomers and assembled into hemichannels, thus questioning their role solely as cell–cell communication channels. Accordingly, mitochondrial connexins have been suggested to play critical roles in the regulation of mitochondrial functions, including potassium fluxes and respiration. However, while much is known about plasma membrane gap junction channel connexins, the presence and function of mitochondrial connexins remain poorly understood. In this review, the presence and role of mitochondrial connexins and mitochondrial/connexin-containing structure contact sites will be discussed. An understanding of the significance of mitochondrial connexins and their connexin contact sites is essential to our knowledge of connexins’ functions in normal and pathological conditions, and this information may aid in the development of therapeutic interventions in diseases linked to mitochondria.