The Mitochondrial Fusion-Related Proteins Mfn2 and OPA1 are Transcriptionally Induced during Differentiation of Bone Marrow Progenitors to Immature Dendritic Cells

Abstract

The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration. These results suggest that the mitochondrial fusion-related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.