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While neurons in early developmental stages possess robust ability for axon growth,mature neurons in the central nervous system (CNS) fail to regrow after axonal injury.Regeneration is a highly energy-demanding process,raising a fundamental question as to whether mitochondrial transport is necessary for mature neurons to meet enhanced metabolic requirements during regeneration.Our previous study demonstrated that syntaphilin (SNPH) acts as a "static anchor" specific for axonal mitochondria (Kang et al.,Cell 2008;Chen and Sheng,JCB 2013).Deleting murine snph results in a substantially increased percentage (~70%) of motile axonal mitochondria in vitro and in vivo.Conversely,over-expressing SNPH abolishes axonal mitochondrial transport.Most interestingly,SNPH is strictly developmentally regulated in the brain: its expression is hardly detectable in embryonic stages,very low before postnatal day 7,and peaks at adult stages.The unique pattern of SNPH ex-pression in the brain and its specific role in anchoring axonal mitochondria allow us to propose an attractive hypothesis:mature neuron-associated decline of mitochondrial transport is an intrinsic mechanism controlling axon regrowth capacity.Thus,snph knockout (KO) mice provide an ideal model to investigate how mitochondrial trafficking and anchoring influenc-es axonal regenerative capacity in mature neurons.Here,we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons.Axonal mitochondrial transport progres-sively declines with maturation.Applying microfluidic culture devices,we found that axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons.Thus,mature neuron-associated increases in SNPH expression and decline of mitochondrial transport cause local energy deficits.Strikingly,enhancing mitochondrial transport via genetic ma-nipulation facilitates regenerative capacity in mature neurons by replenishing healthy mitochondria in injured axons,thereby rescuing energy deficits.An in vivo sciatic nerve crush study further shows that enhanced axonal mitochondrial transport in snph KO mice accelerates axon regeneration.Understanding deficits in mitochondrial trafficking and energy supply in in-jured axons of mature neurons benefits development of new strategies to stimulate axon regeneration.