The lysosomal enzyme receptor protein (LERP) of Drosophila melanogaster is the ortholog of the mammalian cation-independent mannose 6-phosphate (Man 6-P) receptor, which mediates trafficking of newly synthesized lysosomal acid hydrolases to lysosomes. However, flies lack the enzymes necessary to make the Man 6-P mark, and the amino acids implicated in Man 6-P binding by the mammalian receptor are not conserved in LERP. Thus, the function of LERP in sorting of lysosomal enzymes to lysosomes in Drosophila is unclear. Here, we analyze the consequence of LERP depletion in S2 cells and intact flies. RNAi-mediated knockdown of LERP in S2 cells had little or no effect on the cellular content or secretion of several lysosomal hydrolases. We generated a novel Lerp null mutation, LerpF6, which abolishes LERP protein expression. Lerp mutants have normal viability and fertility and display no overt phenotypes other than reduced body weight. Lerp mutant flies exhibit a 30–40% decrease in the level of several lysosomal hydrolases, and are hypersensitive to dietary chloroquine and starvation, consistent with impaired lysosome function. Loss of LERP also enhances an eye phenotype associated with defective autophagy. Our findings implicate Lerp in lysosome function and autophagy.
Photodeoxygenation of dibenzothiophene S-oxide (DBTO) has been suggested as a clean way to generate atomic oxygen in solution. Sulfoxide bond dissociation enthalpies (BDEs) are important to the quantum yield and mechanism of this photodeoxygenation. In this study, BDE of substituted DBTO molecules with various functional groups were determined using M062X/aug-cc-pV(T + d)Z and MP2/aug-cc-pV(T + d)Z levels of theory. The sulfoxide BDE was determined using an isodesmic reaction. The observed effect of substitution was that functional groups with negative σ para values (electron donating) strengthen the sulfoxide bond and that substituents with positive σ para values (electron withdrawing) weaken the sulfoxide bond. The Mulliken charge on sulfur for DBTO and the corresponding dibenzothiophene were identified as a suitable indicator of the predicted S-O BDE. Moreover, steric and hydrogen bonding interactions were found to affect sulfoxide BDE for certain functional groups when located at the 1 or 4 positions of the substituted DBTO.
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