ATG8 conjugation on damaged lysosomes triggers rapid assembly of a protein complex containing TFG, which directs lysosomal membrane repair by recruiting ESCRT proteins to sites of damage.

ATG8 conjugation on damaged lysosomes triggers rapid assembly of a protein complex containing TFG, which directs lysosomal membrane repair by recruiting ESCRT proteins to sites of damage.

Jain et al. review how lysosomes act as signaling hubs that couple nutrient export to sensing pathways controlling growth, stress responses, and organelle crosstalk. They highlight immune- and neuron-specific lysosomal programs that integrate metabolic status and organelle health to shape tissue physiology.

Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

Lange et al. identify a lipid droplet quality control pathway in which FSP1 safeguards stored neutral lipids from lipid peroxidation, thereby preventing the induction of ferroptosis.

The de novo purine synthesis pathway is fundamental for nucleotide production, yet the role of mitochondrial metabolism in modulating this process rem…

Ferroptosis, a regulated form of cell death driven by excessive lipid peroxidation, has emerged as a promising therapeutic target in cancer. Ferroptosis suppressor protein 1 (FSP1) is a critical regul...

Trafficking from the endoplasmic reticulum to the Golgi apparatus comprises the first steps toward the correct localization of 30% of eukaryotic proteins. Coat protein complexes COPII and COPI are inv...

By combining structural biology and evolutionary genomics analyses, the evolution of enzymes over 400 million years is shown to be governed by catalytic function, metabolic network architecture, cost ...

Lysosomes break down macromolecules, clear cellular waste and recycle nutrients such as cystine. We describe a novel mechanism whereby JIP4 regulates lysosomal cystine storage by controlling the abundance of cystinosin (CTNS), the transporter responsible for lysosomal cystine efflux. To this end, JIP4, previously characterized as a motor adaptor and kinase signaling scaffold, suppresses TMEM55B-dependent ubiquitylation of CTNS. Loss of JIP4 reduces CTNS protein levels, leading to lysosomal cystine accumulation and lysosomal storage defects that phenocopy loss of CTNS in both human cells and the renal proximal tubules of JIP4 knockout mice. These phenotypes mirror cystinosis, the lysosomal storage disease caused by CTNS loss-of-function. Our findings thus reveal a fundamental process that controls the efflux of lysosomal cystine and has relevance to understanding human disease arising from JIP4 mutations. ### Competing Interest Statement The authors have declared no competing interest. NIH, AG085824, AG062210, R35GM150619 Michael J. Fox Foundation, https://ror.org/03arq3225, ASAP-000580

Lysosome damage activates multiple pathways to prevent lysosome-dependent cell death, including a repair mechanism involving endoplasmic reticulum (ER…

FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 ...

A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.

Mutations in LRP10, a low-density lipoprotein receptor family member, cause familial Parkinson's disease and dementia with Lewy bodies. However, its direct cellular functions remain largely undefined....

A bacterial endosymbiont of marine algae evolved to an organelle

Random mutagenesis and deep mutational scanning (DMS) are widely used to optimize proteins by oversampling large libraries in microbial cells, selecting cells expressing favorable variants, and sequen...

This work challenges a major assumption in cell biology by showing that lipid bilayers can have drastically different phospholipid abundances between their two leaflets. This lipid abundance asymmetry...

The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once in archaea. We show that uniaxial compression induces clonal mul...

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...