A Missing Mitochondrial Link
Crosslinking mass spectrometry reveals extensive contacts between the ATP synthase F1 head and multiple TCA-cycle enzymes in mouse heart mitochondria.
Crosslinking mass spectrometry has revealed an unexpected structural link between ATP synthase and the tricarboxylic acid cycle in mouse heart mitochondria.
In the new study, Albert Heck’s group and collaborators found that the F1 catalytic head of ATP synthase formed extensive contacts with multiple tricarboxylic acid cycle enzymes, challenging the idea that complex II is the only direct structural bridge between these systems. In-solution crosslinking mass spectrometry captured protein proximities in intact mitochondria, preserving interactions that are difficult to detect with more disruptive biochemical approaches.
The team paired the crosslinking data with quantitative proteomics, complexome profiling, and blue native PAGE. In wild-type mouse hearts, ATP synthase showed stronger connectivity to tricarboxylic acid cycle enzymes than any other oxidative phosphorylation complex, with many of those contacts clustering around the soluble F1 head.
The researchers then examined heart mitochondria from mice lacking LRPPRC, a defect that impairs mitochondrial gene expression and destabilizes ATP synthase. Proteomics and complexome profiling indicated disruption of the membrane-embedded portion of the complex together with accumulation of F1-containing subassemblies. Under those conditions, interactions between the F1 head and tricarboxylic acid cycle enzymes became more prominent, alongside increased association with other metabolic proteins.
The stressed mitochondria also exhibited in vivo binding of ATPase inhibitory factor 1 to the F1 head through its N-terminal inhibitory region, consistent with a shift toward an energy-preserving state that suppresses wasteful ATP hydrolysis.
The authors suggest future work will be required to test what these remodeled interactions mean functionally, and whether they can be targeted in diseases involving impaired ATP synthase activity or stability.
Following Nanoparticles by Their Proteomic Neighbors
Nanozyme proximity labeling distinguishes mitochondria-targeted nanoparticles from non-targeted particles routed mainly toward lysosomal degradation.
A new proximity-labeling workflow has mapped how different nanoparticles move through live cells, showing that mitochondria-targeted iron oxide particles become associated with mitochondrial proteins and trafficking factors, while non-targeted counterparts are routed mainly toward lysosomal degradation.
Imaging can show where particles accumulate, but usually gives only a partial view of the transport process, while standard proteomics disrupts the local protein environment during cell lysis. In the new study, researchers used the peroxidase-like activity of iron oxide nanoparticles to label nearby proteins in situ, creating a proteomic readout of nanoparticle trafficking without the engineered enzyme fusions required in conventional proximity-labeling methods.
The method, called nanozyme proximity labeling, was activated with hydrogen peroxide and labeled proximal proteins within about a minute. After enrichment, liquid chromatography–tandem mass spectrometry was used to identify the surrounding protein networks and compare the intracellular behavior of targeted and non-targeted particles.
Applied to mitochondria-targeted and non-targeted particles, the workflow distinguished two different intracellular fates. The targeted nanoparticles showed roughly 1.5-fold enrichment of mitochondrial proteins and interacted with trafficking factors consistent with mitochondrial anchoring. Non-targeted particles, by contrast, were associated mainly with proteins linked to lysosomal trafficking and degradation, suggesting a more conventional intracellular fate.
The method helps resolve the protein interactions that separate successful targeting from degradation, offering a more specific way to assess how surface design shapes intracellular fate.
Docking Domains and Drug Diversity
The study explains how bacteria generate multiple related histone deacetylase inhibitors from a shared biosynthetic framework.
A long-missing biosynthetic pathway has helped explain how bacteria generate multiple related histone deacetylase inhibitors. In a new study of FR-901375, a depsipeptide related to the approved T-cell lymphoma drug romidepsin, researchers showed that structural diversity in this family depends on docking domains that connect a conserved core biosynthetic system to more variable cap-forming enzymes.
Using bioinformatic searches, the team identified the FR-901375 biosynthetic gene cluster in Pseudomonas chlororaphis subsp. piscium, then confirmed metabolite production in the bacterium. In vitro reconstitution experiments, supported by intact-protein mass spectrometry, showed productive transfer between the core depsipeptide machinery and the enzymes responsible for building the variable cap structure.
"For decades, we've known that bacteria can naturally produce multiple versions of powerful anti-cancer drugs, yet we had no idea how they achieved this,” said first author Munro Passmore in the team’s press release. “This work finally cracks that code.”
To define that interface, the researchers combined AlphaFold modeling with carbene footprinting, mutagenesis, and gene deletion experiments. Together, the data supported a conserved docking interaction that allows different biosynthetic partners to exchange intermediates while preserving productive handoff. The study also suggests that the FR-901375 pathway evolved through duplication and recombination of related biosynthetic elements.
With that docking logic in hand, the authors now plan to test how broadly the same interface can support engineered variants. “Our immediate goal is to build an expanded library of candidates for various cancers where new treatments are urgently needed,” said senior author Greg Challis.
A Seasonal Split in the Arabian Sea
MSI and hyperspectral analysis show that summer and winter monsoons responded differently during rapid postglacial climate change.
A new reconstruction of Arabian Sea sediments suggests that summer and winter monsoons responded differently during the rapid climate shifts that followed the last ice age.
The researchers combined mass spectrometry imaging with hyperspectral imaging and conventional isotope methods to trace past changes in sea-surface conditions, marine productivity, and monsoon-linked environmental signals between about 16,000 and 12,000 years ago. The imaging workflow provided micrometer-scale chemical maps across the sediment layers, helping recover seasonal structure that is usually blurred in lower-resolution paleoclimate records.
That analytical resolution mattered because different proxy signals in the core respond to different components and seasons of the monsoon system. Pairing imaging mass spectrometry with hyperspectral data and isotope measurements allowed the team to compare summer and winter monsoon behavior within the same archive, rather than infer broader climate averages alone.
Summer monsoon variability tracked climate processes in the higher latitudes of the Northern Hemisphere, while the winter monsoon weakened more gradually as global temperatures rose. “Our analyses show that summer and winter monsoons reacted differently during a period of rapid climate change following the last ice age,” said lead author Igor Obreht in the University of Bremen press release.
Periods of weaker winter monsoon activity coincided with increased precipitation outside the main monsoon season, suggesting that winter monsoon weakening changed the timing of rainfall rather than simply reducing it overall. “We have identified a previously unknown inverse relationship between winter monsoon wind strength and non-monsoonal winter precipitation,” said co-author Mahyar Mohtadi.
(Mass) Spectacular and Strange
Particles on the Menu
For restaurant workers, the hazards of the kitchen are usually obvious: heat, knives, pressure, and perhaps even displeased customers. A new study has spotlighted a less visible concern: the air.
Sampling from 18 full-service restaurants in New York City, the study measured particulate matter, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), carbon monoxide, and black carbon across eight-hour shifts. Gas chromatography–mass spectrometry was used to identify airborne VOCs and PAHs, while particulate matter was measured in kitchen and dining areas.
The results were not exactly appetizing. Kitchen particle levels were about four times higher than those in dining areas and nearly ten times higher than outdoor air, with some real-time readings briefly surging far above the shift average. Although the eight-hour values stayed below occupational exposure limits, they still sat well above the World Health Organization’s 24-hour guideline for ambient air.
The chemical findings were less straightforward: PAHs were often below detection, but kitchen air still carried a shifting mix of VOCs linked to cooking, combustion, and cleaning products, including occasional detections of benzene.
For restaurant workers already dealing with long shifts and demanding conditions, the findings highlight another occupational exposure hiding in plain sight. The authors argue that future studies should look more closely at worker health, particle-bound chemicals, ventilation, filtration, and the difference between gas and electric cooking.
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