Lysosomes articles from across Nature Portfolio

The degradation of inner autophagosomal membranes remains poorly understood. Here, Makar et al. show that RNAseK is involved in a lysosomal hydrolase delivery pathway that contributes to autophagosomal membrane degradation.

We show that cytosolic inner mitochondrial membrane vesicles, devoid of outer mitochondrial membrane or mitochondrial matrix, are formed during resting state and directly herniate into lysosomes through pores formed by voltage-dependent anion channel 1 in the outer mitochondrial membrane, thereby allowing their selective removal.

How dsRNAs translocate to the cytosol during soaking RNAi remains unclear. Here, the authors show that the Cl⁻/H⁺ antiporter supports dsRNA-induced LMP and the cytosolic release of dsRNAs.

Reviewer recognition:

The efficiency of antibody-based immune checkpoint blockades could be compromised by the intracellular accumulation of checkpoint proteins. Here authors show that a pH-responsive artificial protein that targets PD-L1 to lysosomal degradation could achieve superior therapeutic effect compared to anti-PD-L1 treatment in mouse models of high microsatellite instability colon adenocarcinoma.

Okreglak et al. explore the molecular mechanisms that link organellar pH dynamics with the cell cycle, and find that vacuolar pH oscillates during cell cycle phases to ensure an adequate supply of amino acids during cell division. This study offers metabolic insight into the fundamental mechanisms that couple amino acid availability to the cell cycle through pH fluctuations.

In this Tools of the Trade article, Nouf Laqtom (at the Abu-Remaileh lab) describes the LysoIP system used to tag and isolate lysosomes for multi-omic approaches and to determine their composition under physiological and pathological states.

Quality control of misfolded glycosylphosphatidylinositol-anchored proteins (GPI-APs) does not occur through ER-associated degradation, as the lipid anchor precludes retrotranslocation across the ER membrane. Instead, different organisms have developed distinct solutions to prevent the accumulation of misfolded GPI-APs.