After nearly two decades at Harvard, neuroscientist Naoshige Uchida is preparing to take on a new role: chair of the Department of Molecular and Cellular Biology (MCB). Uchida, […]

Lipid droplets (LDs) are conserved organelles that buffer lipid storage and stress, yet their dynamics and functions in neurons remain largely unknown. Here, we report activity-dependent dynamics of n...

Thiam and Carpentier review seipin as a conformationally dynamic lipid rheostat that steers lipid fate and preserves cellular metabolic balance.

Mizrak et al. use single-molecule tracking to dissect mechanisms of protein targeting to lipid droplets. They show that nanodomain-based confinement drives selective protein accumulation on lipid drop...

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusi...

Coupling an optogenetic lipid-modifying enzyme with proximity labeling reveals protein networks and mechanisms regulating lipid homeostasis in the membranes of target organelles.

The ExoSloNano system facilitates nanogold probe-based labeling of specific proteins of a wide range of sizes in live cells for cryo-electron tomography and correlative light and electron microscopy s...

The microprotein adipogenin (Adig) is predominantly expressed in adipose tissues. Here, we found that Adig interacts with seipin to form a stable, rigid complex. We present the structure of the seipin...

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

The formation of social hierarchies is a fundamental aspect of group living, reducing conflict and guiding behavior across species—from animals to humans. Yet, the precise neural and molecular […]

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

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

Understanding how proteins interact inside living cells is fundamental to biology. Yet, visualizing these interactions with high precision—and at the scale and condition at which they actually occur—h...

Nobel Laureate and HHMI Investigator Ardem Patapoutian, PhD will deliver the 2025 Bloch lecture. His talk, “May the Force Be With You! Piezo Channels in Mechanosensory Biology,” will […]

Dean Rosenthal, a second-year PhD student in Harvard’s Biological Sciences in Public Health (BPH) program, has been awarded a National Science Foundation Graduate Research Fellowship (GRFP)—one of the...

The LPD-3 complex structure reveals protein–lipid interactions that suggest a model for how the native LPD-3 complex mediates bulk lipid transport and provides a foundation for mechanistic studies of ...

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...

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...

This year, James M Berger, of Johns Hopkins University School of Medicine will return to Harvard to present the Doty Lecture, “Still Unscrambling the Puzzle of Biological Machines: […]

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

This year, MCB will host the annual John M. Prather Lectures in Biology, a series of three talks inspired by a bequest to Harvard by the 19th-century Harvard-trained […]

Mammalian tissues feed on nutrients in the blood circulation. At the organism level, mammalian energy metabolism is comprised of the oxidation, storag…