Open AccessA fragment of adhesion molecule L1 is imported into mitochondria and regulates mitochondrial metabolism and trafficking
Author(s) -
Kristina Kraus,
Ralf Kleene,
Ingke Braren,
Gabriele Loers,
David Lutz,
Melitta Schachner
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.210500
Subject(s) - biology , mitochondrion , microbiology and biotechnology , mitochondrial fusion , myelin , protein subunit , transmembrane protein , transport protein , biochemistry , mitochondrial dna , central nervous system , receptor , neuroscience , gene
The cell adhesion molecule L1 plays important roles in the mammalian nervous system under physiological and pathological conditions. We have previously reported that proteolytic cleavage of L1 by myelin basic protein leads to the generation of a 70 kDa transmembrane L1 fragment (L1-70) that promotes neuronal migration and neuritogenesis. Here, we provide evidence that L1-70 is imported from the cytoplasm into mitochondria. Genetic ablation of L1, inhibition of mitochondrial import of L1-70 or prevention of myelin basic protein-mediated generation of L1-70 lead to reduced mitochondrial complex I activity, impaired mitochondrial membrane potential, fusion, fission, and motility as well as increased retrograde transport. We identified NADH dehydrogenase ubiquinone flavoprotein 2 as a binding partner for L1, suggesting that L1-70 interacts with this complex I subunit to regulate complex I activity. The results of our study provide insights into novel functions of L1 in mitochondrial metabolism and cellular dynamics. These functions are likely to ameliorate the consequences of acute nervous system injuries and chronic neurodegenerative diseases.