Chemical biology approaches have enhanced metabolism research through the detection of key metabolites and altering enzymatic reactions. This themed issue features a collection of articles that explore emerging research areas in the continual interplay between chemical biology and metabolism.

Nicotinamide adenine dinucleotide phosphate (NADPH) is a reducing cofactor present in cytosolic and mitochondrial pools, with each pool requiring distinct NAD+ kinases (NADK and NADK2). NADK2 mediates production of mitochondrial NADP(H) and is essential for proline biosynthesis. To uncover new roles for NADK2 in metabolism, Kim et al. used a cancer dependency map database (DepMap) and identified NADK2

Mitochondria serve as the energy factories of cells, powering various biological processes, and their dysfunction is linked to many types of disease, such as cancer, neurodegenerative diseases and metabolic disorders. For example, mutations in DNA polymerase γ (POLγ), the enzyme responsible for mitochondrial DNA (mtDNA) replication, can cause mtDNA depletion, leading to severe clinical symptoms associated

The mitochondrial cristae — the folds of the inner mitochondrial membrane — undergo structural remodeling during respiration and apoptosis that also triggers outer mitochondrial membrane permeabilization. Such remodeling is likely to influence the composition and potentially the functional roles of the large protein complexes abundant in the cristae. Yet, how cristae remodeling affects the structure

BRCC36 is a Zn2+-dependent JAMM/MPN deubiquitinase (DUB) and is an essential component of the BRCC36 isopeptidase complex (BRISC), which blocks K63-linked ubiquitination and degradation of type I interferon receptor (IFNAR1) to enhance inflammatory signaling. The zinc-binding pocket of BRCC36 is conserved with other JAMM/MPN members, which makes selectively targeting BRCC36 difficult. To identify BRISC

N6-methyladenosine (m6A) is one of the most abundant RNA modifications and has an important role in many biological processes. The major writer for m6A is the METTL3–METTL14 complex, whereby METTL3 acts as the catalytic methyltransferase while METTL14 is thought to determine substrate specificity. However, it is unclear whether the interaction between METTL3 and METTL14 can be regulated to affect m6A

Peptide hormones are processed from larger proteins by endopeptidases and have diverse biological functions. For example, glucagon-like peptide-1 (GLP-1) is well known for regulating blood glucose levels and has been used to treat diabetes and obesity. However, there are a vast number of peptides that are potentially processed by endopeptidases to create functional peptide hormones. Now, Coassolo et

Correction to: Nature Chemical Biology https://doi.org/10.1038/s41589-024-01629-x, published online 23 May 2024.