Phosphorylation of Human TFAM in Mitochondria Impairs DNA Binding and Promotes Degradation by the AAA+ Lon Protease

► cAMP-dependent protein kinase (PKA) serine phosphorylates TFAM within HMG1 ► HMG1 phosphorylation of TFAM impairs DNA binding and transcription activation ► Lon protease selectively degrades DNA-free TFAM and is inhibited by bortezomib ► Lon knockdown stabilizes TFAM in mtDNA-deficient cells and upregulates mtDNA