# PERM1--An Emerging Transcriptional Regulator of Mitochondrial Biogenesis: A Systematic Review
## 3 Results
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Author** & **Model/Intervention** & \multicolumn{2}{c}{**Key Findings**} \\ \hline  & & \(\bullet\) & Increases in PERMI following PGC-1\(\alpha\)/\(\beta\) overexpression are dependent on ERR\(\alpha\); PGC-1\(\alpha\) and ERR\(\alpha\) bind to ERRE2 on the PERM1 promotor. \\  & & \(\bullet\) & PERM1 protein is primarily restricted to nuclear and cytosolic fractions. \\  & & \(\bullet\) & PERM1 overexpression upregulates some (_CKMT2_, _TNN13_, and _GLUT4_), but not all, PGC-1 and ERR targets and does not alter expression of PGC-1 and ERR family members, \\  & C2C12 cells & & suggesting that PERM1 does not act by altering general PGC-1 or ERR levels and activity. \\  & & \(\bullet\) & PERM1 knockdown does not affect basal mtDNA but does reduce basal OxPhos (_mRNA_ and protein) expression, and blunt PGC-1\(\alpha\) induced- increases in mtDNA and OxPhos (_mRNA_ and protein). \\  & & \(\bullet\) & PERM1 knockdown downregulates _CPT1D_ mRNA after PGC-1\(\alpha\) induction. \\ \hline  & Mice & \(\bullet\) & _PERM1_ mRNA and PERM1 protein are highly expressed in skeletal muscle, heart, and, to a lesser degree, brown adipose tissue. \\  & & \(\bullet\) & _PERM1_ increases in quadriceps muscle following 5 weeks of voluntary running. \\ \cline{2-3}  & Human & \(\bullet\) & Skeletal muscle _PERM1_ mRNA increases following one bout of endurance exercise (60 min @ 70\%O_{2 max}\) and is reduced in the muscles of patients with ALS. \\ \hline  & [21] & Human & \(\bullet\) & An increased abundance of PERM1 and CKMT2 proteins is found in the skeletal muscle, at rest, of endurance-trained subjects compared with untrained/sedentary individuals. \\  & & \(\bullet\) & PERM1 does not impact on muscle morphology; fiber size, or fiber type. \\  & & \(\bullet\) & PERM1 increases mtDNA, OxPhos protein/activity, CS and SDH activity, mitochondrial content, maximal mitochondrial respiration, capillary density, and vascularization (VEGFA protein expression). \\
[11] & Muscle specific PERM1 & \(\bullet\) & PERM1 increases PGC-1\(\alpha\), ERR\(\alpha\), SIRT3 _mRNA_, protein levels, the expression of _TFAM_, _TF2M_, _ENDOG_, _GLUT4_, and _CPT1B_ genes, and MYOGLOBIN protein expression. \\  & & \(\bullet\) & PERM1 increases p-93 MAPK during active hours and enhances fatigue resistance in skeletal muscle. \\ \cline{2-3}  & Primary Myotubes & \(\bullet\) & PERM1 increases p-93 MAPK in primary myotubes. \\ \hline  & & \(\bullet\) & Endurance exercise training leads to PERM1 protein upregulation in the skeletal muscle of patients with type 2 diabetes mellitus. \\
[22] & Human & \(\bullet\) & PERM1 is homogenously distributed in type I and type II muscle fibers of patients with type 2 diabetes mellitus prior to exercise training. \\ \hline  & [23] & Human & \(\bullet\) & Upregulation of skeletal muscle _PERM1_ mRNA and _PGC-1a_ mRNA occurs following an acute bout of exercise (three all-out cycle sprints of 30 s duration interspersed with 20 min recovery). \\ \hline  & Mice & \(\bullet\) & PERM1 co-precipitates with CaMKII in mouse TA muscles. \\  & & \(\bullet\) & PERM1 activation of _MEF2_ promotor is CaMKII-dependent. \\ \hline  & & \(\bullet\) & In the skeletal muscle of mice performing acute exercise, PERM1 knockdown leads to: \\  & & \(\bullet\) & Reduced exercise-mediated increases in p-CaMKII and p-p38 MAPK protein expression. \\  & & \(\bullet\) & Reduced induction of _PGC-1a_, _NR4A3_, and _GAD45G_ and increased induction of _ATF3_ and _MT2_ gene expression. \\  & & \(\bullet\) & In the skeletal muscle of mice performing 4 weeks of voluntary wheel running, PERM1 knockdown leads to: \\  & in mice & \(\bullet\) & Decreased training induces an increase in mtDNA content. \\
[13] & & \(\bullet\) & Decreased protein levels of all OxPhos complexes in both sedentary (SED) and trained (TR) mice. \\  & & \(\bullet\) & Reduced activities of complex IV, SDH, and citrate synthase in both SED and TR mice. \\  & & \(\bullet\) & abolished training induces increases in myoglobin, CKMT2, and CPT1B proteins, decreases in the protein levels of PGC-1\(\alpha\), and increases in ERR\(\alpha\) and SIRT3 proteins in both SED and TR muscles. \\ \cline{2-3}  & Mice—Diet induced & \(\bullet\) & Skeletal muscle _PERM1_ mRNA and protein levels decreases in diet-induced obese mice. \\  & Obesity & \(\bullet\) & Skeletal muscle _PERM1_ mRNA levels decrease in muscular dystrophy patients and in the tibialis anterior muscle of mouse models of Duchenne muscular dystrophy. \\ \hline  & [24] & Mice & \(\bullet\) & _PERM1_ mRNA and protein levels are highly expressed in skeletal muscle. \\ \hline  & [25] & C2C12 cells & \(\bullet\) & PERM1 is located in the outer mitochondrial membrane. \\ \cline{2-3}  & Mice & \(\bullet\) & Enhanced protein synthesis of PERM1 occurs in the skeletal muscle of denervation-induced atrophy mouse. \\ \hline \hline \end{tabular}
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