Diabetes Metab J.  2021 Nov;45(6):853-865. 10.4093/dmj.2021.0138.

Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases

• Koh JH
• Kim YW
• Seo DY
• Sohn TS

• KMID: 2522724
• DOI: http://doi.org/10.4093/dmj.2021.0138

Abstract

Tissues actively involved in energy metabolism are more likely to face metabolic challenges from bioenergetic substrates and are susceptible to mitochondrial dysfunction, leading to metabolic diseases. The mitochondria receive signals regarding the metabolic states in cells and transmit them to the nucleus or endoplasmic reticulum (ER) using calcium (Ca²⁺) for appropriate responses. Overflux of Ca²⁺ in the mitochondria or dysregulation of the signaling to the nucleus and ER could increase the incidence of metabolic diseases including insulin resistance and type 2 diabetes mellitus. Mitochondrial transcription factor A (Tfam) may regulate Ca²⁺ flux via changing the mitochondrial membrane potential and signals to other organelles such as the nucleus and ER. Since Tfam is involved in metabolic function in the mitochondria, here, we discuss the contribution of Tfam in coordinating mitochondria-ER activities for Ca²⁺ flux and describe the mechanisms by which Tfam affects mitochondrial Ca²⁺ flux in response to metabolic challenges.

Keyword

Calcium; Cell nucleus; Diabetes mellitus, type 2; Endoplasmic reticulum; Mitochondria; TFAM protein