Consistent with the increased heart-to-body-weight ratio of Polg-/mut; Tfam+/+ mice (Figure 1C), the expression of Natriuretic Peptide A (Nppa), a marker for heart failure, and Mthfd2, as described above a marker for OXPHOS dysfunction, were increased, whereas there was no change in mRNA levels for Atf4 and Atf5 (Figure 4C). Here, TFAM is linked to heart failure.