Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.Investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in four independent weight-loss studies.The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n=261) and 6-month weight maintenance (n=121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n=172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in two studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n=19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n=49) and 5-year (n=37) follow-up.Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; Ingenuity Pathway Analyses (IPA) z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all p<0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, p<0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, p<0.001).Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.