Biology subjects

Paavilainen, V. O.

Publications and source records attributed to Paavilainen, V. O..

3 recordsLinked to original sources

bioRxiv2026

Solvent specific bioactivities of cone, leaf, and stem extracts from a native Finnish wild hop

The genetically authenticated Finnish hop genotype LUKE 2541 obtained from wild was evaluated for antibacterial, anti-inflammatory, and anticancer activities. Water extracts from hop cones inhibited the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, with MIC values of 0.094- 0.188mg/mL, whereas Gram-negative strains showed limited sensitivity. In LPS-primed THP-1 cells, both IPA and IPA-Control extracts reduced reactive oxygen species formation in a dose-dependent manner, exhibiting similar IC50 values (50.41{micro}g/mL and 35.41{micro}g/mL). This hop genotype also displayed clear tissue- and solvent-dependent antiproliferative effects in human cancer cell lines. Bioactivity was strongly enriched in hop cones and predominantly associated with non-polar extracts, particularly hexane and dichloromethane fractions, which produced marked, dose-dependent reductions in cell viability. In contrast, aqueous and methanolic extracts were largely inactive, underscoring the critical importance of extraction chemistry and tissue selection. Sensitivity varied among cancer cell lines, with colorectal cells generally more responsive and leukemia cells less affected, highlighting cell-specific susceptibility. Further research is needed to elucidate underlying mechanisms, determine selectivity toward non-malignant cells, and identify the active compounds responsible for all in all investigated effects.

biochemistry↗

bioRxiv2023

The Sec61/TRAP Translocon Scrambles Lipids

Cell growth relies on the rapid flip-flop of newly synthesized lipids across the ER membrane. This process is facilitated without the need for ATP by specific membrane proteins--scramblases--a few of which have been very recently identified in the ER. We have previously resolved the structure of the translocon-associated protein (TRAP) bound to the Sec61 translocon in the ER membrane, and found this complex to render the membrane locally thinner. Moreover, Sec61 and TRAP each contain a crevice rich in polar residues that can shield a lipid head group as it traverses the hydrophobic membrane environment. We thus hypothesized that both Sec61 and TRAP act as ER scramblases. Here, we characterized the scrambling activity of Sec61 and TRAP using extensive molecular dynamics simulations. We observed that both Sec61 and TRAP efficiently scramble lipids via a credit card mechanism. We analyzed the kinetics and thermodynamics of lipid scrambling and demonstrated that local membrane thinning provides a key contribution to scrambling efficiency. Both proteins appear seemingly selective towards phosphatidylcholine lipids over phosphatidylethanolamine and phosphatidylserine, yet this behavior rather reflects the trends observed for these lipids in a protein-free membrane. The identified scrambling pathway in Sec61 structure is physiologically rarely unoccupied due to its role in protein translocation. Furthermore, we found that the scrambling activity of this pathway might be impeded by the presence of ions at a physiological concentration. However, the trimeric bundle of TRAP{beta}, TRAP{gamma}, and TRAP{delta} might provide scrambling activity insensitive to the functional state of the translocon and the solvent conditions.

biophysics↗

bioRxiv2023

Peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved.

Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, glycolysis, and biosynthesis of sterols and ether lipids. Defects in peroxisome biogenesis result in severe neurological diseases, such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and myelopathies. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter ER in both WT and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. However, in PEX3 KO cells, which lack peroxisomes as well, the endogenous TA protein, ACBD5, does not target mitochondria, suggesting that PEX3 plays an important role in targeting of peroxisomal TA proteins to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the endoplasmic reticulum (ER), peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes. Instead, mitochondria can play a role in the targeting of TA proteins to peroxisomes.

cell biology↗