Proposed mechanism. (a) DHA increased ROS production, mainly O2●−, leading to oxidative damage that may trigger mitochondrial fusion as tentative to restoration of organelle function. Also, such fatty acid increased lipid accumulation which may increase ROS. In this context, we hypothesize that DHA raised oxidative stress, therefore impairing mitochondrial function, which then stimulated organelle fusion and led to area and perimeter increase as well as the recovery of OXPHOS, but not MBRC. In addition, DHA also inhibited AKT activation which may be related to increase in oxidative damage and decrease in cell proliferation. (b) MLT decreased ROS production, both O2●− and H2O2, and improved OXPHOS which may be associated to AKT/mTOR inactivation. (c) DHA increased oxidative damage which was not neutralized by MLT, but together (DM) amplified the antiproliferative effect probably due to AKT and ERK1/2 regulation. MLT, alone or coincubated, stimulated ERK1/2 activation as well as androgen uptake, but the mechanism is not clear. Also, MLT coincubated with DHA-stimulated GSTP1 expression probably due to ROS increase. Legend: DHA: docosahexaenoic acid; MLT: melatonin; DM: coincubation; O2●−: superoxide anion production; H2O2: hydrogen peroxide; ATP: adenosine triphosphate; OXPHOS: oxidative phosphorylation; MBRC: mitochondrial bioenergetics reserve capacity; ROS: reactive oxygen species. Dashed lines, mechanism proposed based on the literature; solid lines, effects and correlations based on observed results.