Sensing and Regulating Cellular Energy Production

Western blot showing that yeast with impaired production of mitochondrial acetyl-CoA due to loss of the mitochondrial pyruvate carrier (mpc1) have impaired assembly of respiratory complexes.

Cells must decide when to expand mitochondrial capacity to accommodate increased energy demands. Rutter, Winge, and colleagues have shown that the ancient mitochondrial fatty acid synthesis system has a profound and unexpected regulatory role in driving mitochondrial biogenesis. The team showed that a potential cause originates from the scaffold protein, Acyl Carrier Protein 1 (ACP1), which functions in the building of fatty acids and also binds and activates a series of proteins required for mitochondrial biogenesis.

The binding of proteins related to this biogenesis requires that ACP1 is acylated. ACP1 acylation requires and is rate-limited by the cofactor acetyl-CoA, which acts as the universal fuel for respiration as well as the substrate for fatty acid synthesis. Thus, this system provides an elegant mechanism for sensing and creating an increased respiratory capacity to meet demand. Thus, eukaryotic cells adjust the level of active electron transport chain complexes to match the level of acetyl-CoA “fuel” available.


Issues Icon

The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. Van Vranken JG, Jeong MY, Wei P, Chen YC, Gygi SP, Winge DR, Rutter J. Elife. 2016 Aug;5. pii: e17828.

Issues Icon

ACP acylation is an Acetyl-CoA-dependent modification required for electron transport chain assembly. Van Vranken JG, Nowinski SM, Clowers KJ, Jeong MY, Ouyang Y, Berg JA, Gygi JP, Gygi SP, Winge DR, Rutter J. Molecular Cell. 2018 Aug;71(4):567.