The variety of mitochondrial morphology in healthy and diseased cells can be explained by regulated mitochondrial fusion. Previously, a mitochondrial outer membrane fraction containing fusogenic, aluminum fluoride (AlF₄)-sensitive GTP-binding proteins (mtg) was separated from rat liver (J. D. Cortese, Exp. Cell Res. 240: 122-133, 1998). Quantitative confocal microscopy now reveals that mtg transiently increases mitochondrial membrane potential () when added to permeabilized rat hepatocytes (15%), rat fibroblasts (19%), and rabbit myocytes (10%). This large mtg-induced increment is blocked by fusogenic GTPase-specific modulators such as guanosine 5'-O-(3-thiotriphosphate), excess GTP (>100 µM), and AlF₄, suggesting a linkage between and mitochondrial fusion. Accordingly, stereometric analysis shows that decreasing or ATP synthesis with respiratory inhibitors limits mtg- and AlF₄-induced mitochondrial fusion. Also, a specific G protein inhibitor (Bordetella pertussis toxin) hyperpolarizes mitochondria and leads to a loss of AlF₄-dependent mitochondrial fusion. These results place mtg-induced changes upstream of AlF₄-induced mitochondrial fusion, suggesting that GTPases exert -dependent control of the fusion process. Mammalian mitochondrial morphology thus can be modulated by cellular energetics.

confocal microscopy; G protein; hepatocyte; pertussis toxin; signal transduction; single-cell imaging

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