Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria

The molecular motor kinesin is an ATPase that mediates plus end-directed tr ansport of organelles along microtubules. Although the biochemical properti es of kinesin are extensively studied, conclusive data on regulation of kin esin-mediated transport are largely lacking. Previously, we showed that the proinflammatory cytokine tumor necrosis factor induces perinuclear cluster ing of mitochondria, Here, we show that tumor necrosis factor impairs kines in motor activity and hyperphosphorylates kinesin light chain through activ ation of two putative kinesin light chain kinases. Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, ind icating their functional relationship. These data provide evidence for dire ct regulation of kinesin-mediated organelle transport by extracellular stim uli via cytokine receptor signaling pathways.