TFAM (Transcription Factor A, Mitochondrial; aka TCF6) is a member of the high-mobility group (HMG) proteins because it contains two HMG boxes. TFAM is a transcription factor for mitochondrial DNA (mtDNA), and enhances mtDNA transcription in a promoter-specific fashion in the presence of mitochondrial RNA polymerase and transcription factor B. Because the majority of ATP production depends on the mitochondrial respiratory chain, maintenance of the mitochondrial genome is critical for normal health. TFAM plays an essential role in the maintenance of mtDNA and thus, ATP production. TFAM binds to mtDNA both nonspecifically and in a sequence-specific manner. It is known to have a dual effect on mtDNA: protection of mtDNA and initiation of transcription from mtDNA. TFAM attenuates age-dependent impairment of the brain by preventing oxidative stress and mitochondrial dysfunctions in microglia.