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The conventional view of peroxisomal biogenesis has assumed that it is under the transcriptional regulation by PPAR. However, recent studies in hepatic cells have shown that the transcriptional co‐activator, PGC‐1α, can induce peroxisomal gene expression and abundance in a PPAR‐independent fashion. Also, metabolic linkage between mitochondria and peroxisomes may converge in terms of lipid metabolism. It is unknown whether the regulatory mechanism of peroxisomal biogenesis is through the same node as mitochondrial biogenesis in human skeletal muscle and whether fatty acid metabolism is affected. Therefore, we hypothesized that PGC‐1α acts as a biological “driver” for both peroxisomal and mitochondrial biogenesis in human skeletal muscle, leading to metabolic interactions in terms of fatty acid oxidation. Human skeletal muscle cells from vastus lateralis biopsies of lean donors (BMI= 23.6 ± 1.5 kg/m 2 , age=26.7 ± 3.5 years, n=3) were exposed to adenovirus encoding PGC‐1α or GFP at day 4 post differentiation and harvested at day 7. Peroxisomal biogenesis proteins (peroxins) and genes (PEXs) responsible for proliferation and function were assessed by western blot and quantitative real time‐PCR. 1‐ 14 C lignoceric acid, necessarily oxidized first by peroxisomes, was used to assess mitochondrial oxidation of peroxisomal derived fatty acid metabolites. Results Following overexpression of PGC‐1α (protein increased 9.7 fold) 1) peroxisomal exclusive PMP70 and mitochondrial citrate synthase protein content were elevated 3 and 2.8 fold respectively (P<0.05) and PEX19 protein increased by 43% compared to the ad‐GFP controls 2) PGC‐1α, PMP70, PEX19 and a peroxisomal β‐oxidation enzyme, peroxisomal acyl‐coenzyme A oxidase 1, mRNA content were increased by 34.7, 4, 1.3, and 1.5 fold respectively (P<0.05) and 3) A concomitant 2.5‐fold increase in peroxisomal derived lignoceric acid metabolite oxidation by mitochondria was observed. Conclusion In addition to the proliferative power on mitochondria, PGC‐1α is responsible (at least in part) for regulating peroxisomal biogenesis accompanied by elevations in the functional interactions of peroxisomes with mitochondrial lipid disposal in human skeletal muscle. Support or Funding Information Supported in part by a seed grant from the Diabetes Obesity Institute, East Carolina University (RNC), NIH DK 056112(JAH), NIH 1R15HL113854‐01A1 (RCH)