# 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
[12] & Mice & \(\bullet\) & Increased expression of _PERM1_ mRNA in heart tissue. \\ \hline PERM1 gain-of-function & \(\bullet\) & PERM1 overexpression represses the _PGC-1a_ gene (decreased PGC-1\(\alpha\) promoter activity and _mRNA_ levels) and increases PGC-1\(\alpha\) protein levels. \\  & in cardiomyocyteocytes & \(\bullet\) & PERM1 has the capacity to increase ERR response element (ERRE) activity. \\ \hline PERM1 knockdown in & \(\bullet\) & Decreased PGC-1\(\alpha\) protein, followed by decreased levels of _PGC-1a_ mRNA. \\  & in- & _PERM1_ mRNA downregulation, suggesting that _PERM1_ is a target gene of _SMYD1_. \\  & myocytes & & \\ \hline [PERSON] et al., 2020[31] & & \(\bullet\) & Downregulation of ERR\(\alpha\) and PGC-1\(\alpha\) proteins. \\  & & \(\bullet\) & Downregulation of the tricarboxylic acid (TCA) cycle enzymes (Sdhb, Idh2), the subunits of protein complexes comprising the electron transport chain (ETC) (Nüdrußs, Nüdrußs, Cox5a, Cox8a, Cox6a, Cox6a, Cox6a, Cox6a, Cox6a, Cox6a, Cox6a, Cox61), the glycolytic enzymes (Eno3, Pdgdh). \\  & 2020[31] & \(\bullet\) & Upregulation of genes involved in the biosynthesis of amino acids (Psph, Pycr2), sphingolipid metabolism (Gnaic2, Pix3 Ca, Asa2, Cers5, Kdsr, Sgms1), and the phosphatidylinositol signaling system (Inpp5k, Ipmk, Mtm1, Pika3 Ca). \\  & myocytes & \(\bullet\) & PERM1 knockdown in cardiomyocytes leads to the downregulation of genes encoding the ETC subunits (_Nüdrußt1, Nüdüs1_), the TCA cycle (_Cs, Sdh3b, Idh3b_), and the enzymes and transporters involved in FAO (_Cpt1b_, _MCAD_, _Aox1_) and glucose utilization (_Cult4_, _Pdhb_). \\  & & \(\bullet\) & Downregulation of _ERRa_, _PGC-1a_, _PPARa_, and _NR1_. \\  & & \(\bullet\) & Reduced basal respiration rate and ATP production, suggesting that PERM1 is required to maintain mitochondrial energetics in cardiomyocytes. \\ \hline PERM1 gain-of-function & \(\bullet\) & Upregulation of _ERRa_, _Nüdrußt1_, _Nüdüs8_ (Complex I), ATP5a (Complex VI), _CPT1b_, and _CPT2_ (fatty \\ myocytes & & \(\bullet\) & Credit \(\beta\)-oxidation). \\ \hline Neonatal rat ventricular myocytes treated with & \(\bullet\) & Under pressure overload, neonatal ventricular myocytes demonstrate lower _PERM1_, _ERRa_, and _PGC-1a_. \\  & phenylephrine & \(\bullet\) & Under pressure overload, when _PERM1_ expression is maintained in neonatal ventricular \\  & (hypertrophic stress/ pressure overload model) & & myocytes, the expression of _ERRa_ and some _OxPlus_ genes is restored, thus preventing \\ \hline Mouse failing hearts & \(\bullet\) & Decreased expression of PERM1 protein in cardiac tissue from failing hearts. \\ \hline Human failing hearts & \(\bullet\) & Cardiac tissue from failing hearts demonstrates reduced expression of PERM1 protein. \\ \hline  & & \(\bullet\) & PERM1 _mRNA_ and protein levels are highly expressed in heart tissue. \\ \hline  & & \(\bullet\) & _PERM1_ is downregulated in the heart tissue of ERRy knockdown mice. \\ \hline  & & \(\bullet\) & PERM1 gain-of-function increases mitochondrial DNA content, OxPhos protein levels, and maximal oxygen consumption. \\  & & \(\bullet\) & PERM1 can improve both mitochondrial biogenesis and oxidative metabolism by modifying \\  & & \(\bullet\) & PGC-1\(\alpha\) and ERR levels and, consequently, its specific targets. \\  & & \(\bullet\) & PERM1 regulates PGC-1/ERR targets (_PGC-1a_, _ERROR_, _ERRa_, _TERb_, _STER3_, and _ENDOG_) and \\  & & \(\bullet\) & genes essential for electron transfer (_CYTCI and IDH3A_) and energy transduction \\  & & \(\bullet\) & _PERM1_ has the capacity to prevent the cellular damage generated by hypoxia reoxygenation (ischemia–reperfusion injury model) through the regulation of OxPhos proteins. \\ \hline  & & \(\bullet\) & PERM1 protein is more predominant in the ventricular tissue, specifically within the sarcoplasmic reticulum and mitochondrial fraction. \\  & & \(\bullet\) & Developing hearts from mice demonstrate upregulated PERM1 and OxPhos proteins and \\  & & \(\bullet\) & PERM1 interacts with PGC-1\(\alpha\), improves ERR-dependent transcriptional activity, and enables \\  & & \(\bullet\) & _PERM1_, _PGC-1s_ (\(\alpha\) and \(\beta\)), and _ERRs_ (\(\alpha\) and \(\gamma\)) increase continuously from cardiac development to birth. \\  & & \(\bullet\) & Decreased _PERM1_ mRNA and protein detected in heart failure model are associated with cardiac dysfunction. \\ \hline Human & \(\bullet\) & Ventricular tissue from patients with dilated cardiomyopathy demonstrate reduced expression of PERM1 protein. \\ \hline \hline \end{tabular}
\end{table}