The mitochondrial calcium uniporter is widely accepted as the primary route of rapid calcium entry into mitochondria, where increases in matrix calcium contribute to bioenergetics but also mitochondrial permeability and cell death. Hence, regulation of uniporter activity is critical to mitochondrial homeostasis. The uniporter subunit EMRE is known to be an essential regulator of the channel-forming protein MCU in cell culture, but EMRE’s impact on organismal physiology is less understood. Here we characterize a mouse model of EMRE deletion and show that EMRE is indeed required for mitochondrial calcium uniporter function in vivo. EMRE–/– mice are born less frequently; however, the mice that are born are viable, healthy, and do not manifest overt metabolic impairment, at rest or with exercise. Finally, to investigate the role of EMRE in disease processes, we examine the effects of EMRE deletion in a muscular dystrophy model associated with mitochondrial calcium overload.
Bibliographical noteFunding Information:
We are grateful to Michele Allen, Audrey Noguchi, and Morteza Peiravi in the NHLBI Murine Phenotyping Core for help with mouse phenotyping, and Zu-Xi Yu in the NHLBI Pathology Core for assistance with histology. We thank Albert Sek, Helene Rosenberg, and Lee Weinstein for generously providing mice, as well as Baylor, Sanger, Harwell, the EUCOMM consortium, and the MMRRC for the EMRE conditional knockout mice. We are grateful to the members of the Finkel and Murphy labs for thoughtful discussions and feedback. This work was supported by NIH intramural funds, a Leducq Transatlantic Network grant (to EM), and NIH grants 1R01HL142589 (to TF), 1FI2GM117605 (to JCL), and 1K22HL137901 (to JCL).
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Intramural