PKA activators rapidly induce mitochondrial fusion.

TMRM or MitoTracker-stained PC12 cells (A–C) or hippocampal neurons (D) were treated for the indicated times with either vehicle or the listed compounds and mitochondrial morphology was quantified by blinded comparison to reference images (B–D, means ± S.E.M.). (A) Representative epifluorescence images show formation of interconnected mitochondria upon treatment of PC12 cells with forskolin/rolipram (forsk/roli, 20 µM/1 µM, 3 h). In the representative experiment shown in (B), rapid mitochondrial elongation by 50 µM forskolin is not affected by 100 µg/ml cycloheximide to inhibit protein synthesis. Long-term (20 h) forskolin or a cell-permeant cAMP analog (200 µM cpt-cAMP) promotes mitochondrial fusion in PC12 cells (C) and hippocampal neurons (D); summaries of three independent experiments with 20–30 cells per condition are shown.