bims-cesemi 2026-08-16 papers

Cell Metab. 2026 Aug 04. pii: S1550-4131(26)00239-1. [Epub ahead of print]38(8): 1518-1520

Methionine tuning for health without frailty.

Amanda Garrido, Nathan L Price, Rafael de Cabo.

Dietary protein quality, not merely quantity, shapes metabolic health and aging trajectories. Fanti et al. show that moderate methionine supplementation to a low-protein, Mediterranean-inspired diet activates a GH-GLP-1-FGF21 axis that reduces adiposity and frailty without caloric restriction; their findings provide a mechanism for why traditional plant-rich diets may promote longevity while sometimes compromising physical robustness.

DOI: https://doi.org/10.1016/j.cmet.2026.06.013

Cell Rep. 2026 Aug 03. pii: S2211-1247(26)00870-3. [Epub ahead of print]45(8): 117792

Phosphatidylserine synthesis tunes IP3R-mediated ER Ca2+ release via phospholipid homeostasis.

Yifan Zhou, Meng Diao, Yaqiang Liu, Kangmin He, Xiao Yang, Mei Ding, Xun Huang.

Regulation of phospholipid composition is essential for cellular homeostasis. Phosphatidylserine (PS) synthesized in the endoplasmic reticulum (ER) plays critical roles in the plasma membrane and endolysosomal system. Although aberrant PS metabolism is linked to diseases, its cellular effects remain poorly understood. Here, we reveal a conserved role for PS in maintaining Ca2+ homeostasis. PS deficiency in Drosophila leads to mitochondrial damage, which is reversed by reducing inositol 1,4,5-trisphosphate receptor (IP3R)-mediated ER Ca2+ release. Notably, in mammalian cells with pathological PS levels-either deficiency or excess as in Lenz-Majewski syndrome-IP3R activation leads to oscillatory or reduced ER-surface Ca2+ release, contrasting with steady-state conditions. Manipulating phospholipid composition via the phosphatidylethanolamine (PE)-SREBP axis in Drosophila and the phosphatidylcholine (PC)-SREBP axis in mammals normalizes IP3R-mediated Ca2+ release during PS deficiency. These findings establish modulated ER Ca2+ release as a key function of PS and suggest therapeutic strategies for treating lipid metabolic disorders.

Keywords: CP: cell biology; CP: metabolism; Ca(2+); ER; IP(3)R; mitochondrion; phosphatidylserine

DOI: https://doi.org/10.1016/j.celrep.2026.117792

Nat Cell Biol. 2026 Aug;28(8): 1612-1625

Advanced imaging of membrane contact sites.

Riccardo Filadi, Ambra Bertocco, Michela Rossini, Paola Pizzo.

Organelle membrane contact sites (MCSs) coordinate key cell activities and their alterations are associated with several high-incidence disorders, prompting an increasing interest in their study. However, the investigation of MCSs is challenging, mostly because of their nanometric size and dynamic nature. Here we highlight the methods that are available for analysing MCSs. We focus on advanced imaging techniques and discuss their advantages and limitations, providing practical guidance for researchers approaching this field. We propose to study MCSs through a combination of different methodologies, complementing their visualization with investigation of the associated functions. To this end, we also discuss the need to develop innovative biosensors.

DOI: https://doi.org/10.1038/s41556-026-02003-w

Cell Rep. 2026 Aug 14. pii: S2211-1247(26)00935-6. [Epub ahead of print]45(8): 117857

Succinate and its carrier Sfc1 mediate metabolic control of mitochondrial protein import by the TIM23 translocase.

Koyeli Das, Rituparna Samanta, Tamar Ziv, Johannes M Herrmann, Bella Kalderon, Ophry Pines.

Tim23 is an essential component of the mitochondrial inner membrane translocase and Sfc1 is a carrier that exchanges succinate for fumarate across that membrane. Sfc1 and succinic acid availability regulate dual targeting of fumarase and aconitase by facilitating mitochondrial import of their newly synthesized precursors, as shown by pulse-chase experiments. Here, we show that Sfc1 associates with Tim23 in vivo, and succinate modulates this association, which in turn affects mitochondrial protein import. Physical interaction between Tim23 and Sfc1 was proven by co-immunoprecipitation, bimolecular fluorescence complementation (BiFC) and biotin-based proximity labeling (TurboID). Proximity labeling and structural modeling-informed mutagenesis allowed us to dissect the carrier activity of Sfc1 from its function as a TIM23 regulator. We performed Rosetta-MP docking of Sfc1 and Tim23 to envisage the interface. Thus, our findings show that metabolites can regulate mitochondrial import and adjust the segregation of key metabolic enzymes between the cytosol and mitochondria.

Keywords: CP: cell biology; CP: metabolism; Tim23; aconitase; dual targeting; fumarase; glyoxylate shunt; metabolic signaling; metabolites; mitochondrial protein import; succinate-fumarate carrier; tricarboxylic acid cycle

DOI: https://doi.org/10.1016/j.celrep.2026.117857