bims-miptne 2026-06-14 papers

J Biol Chem. 2026 Jun 12. pii: S0021-9258(26)02116-2. [Epub ahead of print] 113244

Mitochondrial permeability transition in redox homeostasis and ferroptosis.

Mitochondria are major sources of intracellular reactive oxygen species (ROS), and act as central signaling hubs in maintaining homeostasis of cellular oxidative states. Mitochondrial permeability transition (MPT) is coordinately mediated by mitochondrial outer membrane permeabilization (MOMP) and opening of the permeability transition pore (PTP). MPT is highly sensitive to ROS, and serves as a critical checkpoint in redox balances and cell death. This review will summarize the regulatory systems of mitochondrial and intracellular redox homeostasis, as well as the recent advances in understanding of MPT regulatory mechanisms. Furthermore, this review highlights the functional roles of MPT in redox homeostasis and ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death. The PTP is a critical molecular switch, which can convert from a defender against mitochondrial redox stress and cell death processes, including specifically iron-dependent, lipid peroxidation-driven cell death, known as ferroptosis, into a ROS amplifier and cell death promoter depending on its open states. MOMP causes the uncoupling of the mitochondrial respiratory chain, and increases ROS production, leading to oxidative stress. The most recent work suggests that the interplay between MTCH2 and F-ATP synthase coordinates MOMP and the PTP opening to mediate the occurrence of MPT. This review provides insight on molecular switches that regulate MPT, determining redox state and cell death.

Keywords: ferroptosis; mitochondria; mitochondrial permeability transition; redox homeostasis; the permeability transition pore

DOI: https://doi.org/10.1016/j.jbc.2026.113244

Nat Commun. 2026 Jun 12.

Nitrate-Sialin2 axis couples ER-mitochondrial calcium signaling with fatty acid metabolism to drive white adipose browning.

Ou Jiang, Zichen Cao, Sihan Kong, Qibing Wu, Tianyi Zhang, Xinyue Chen, Bo Zhou, Yao Feng, Songyue Wu, Jinsong Wang, Mo Chen, Xiaoyu Li, Songlin Wang.

White adipose browning is a promising route to restore energy balance; however, how inorganic anion signals engage intracellular organelle networks to drive this process remains unclear. Here, we identify Sialin2 as a nitrate sensor that converts dietary nitrate into a spatially confined thermogenic program by coupling ER-mitochondria Ca2+ transfer with lipid routing into mitochondrial oxidation. Sialin2 localizes to mitochondria and the endoplasmic reticulum (ER), where it strengthens ER-mitochondria contacts and engages the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter 1 (MCU1) conduit to enhance inducible mitochondrial Ca2+ uptake. In parallel, Sialin2 associates with lysosomal acid lipase (LIPA), acyl-CoA synthetase long-chain family member 3 (ACSL3), and carnitine palmitoyltransferase 1 A (CPT1A) to channel lipid-droplet-derived fatty acids into β-oxidation, thereby fueling the tricarboxylic acid cycle and uncoupling protein 1 (UCP1)-dependent respiration. Loss of Slc17a5 abolishes nitrate-evoked browning and metabolic benefits, whereas nitrate supplementation improves adipose thermogenesis and systemic metabolic indices in male mice with diet-induced obesity without adrenergic stimulation. Together, these findings identify an organelle-specific nitrate-sensing mechanism that couples inorganic anion signalling to substrate routing in adipocytes and establish a non-hormonal pathway for restoring metabolic homeostasis.

DOI: https://doi.org/10.1038/s41467-026-74256-w

Nature. 2026 Jun 10.

Mitochondria directly interact with the nuclear pore complex.

Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria-nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout, RANBP2 truncation or site-directed mutagenesis of RANBP2-VDAC1 interacting amino acids resulted in reduced mitochondria-nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed.

DOI: https://doi.org/10.1038/s41586-026-10588-3

iScience. 2026 Jun 19. 29(6): 116055

Mapping the transcriptional diversity of calcium signaling in the mouse and human brain.

Ibrahim Al Rayyes, Lauri Louhivuori, Ivar Dehnisch Ellström, Erik Smedler, Per Uhlén.

Calcium (Ca2+) signaling is a key regulator of brain function and development. Here, we comprehensively analyze the Ca2+ signaling transcriptome in the adult mouse brain and the developing human brain to reveal the basis of signaling specificity. We show that neurons organize into non-stochastic Ca2+ states that reflect cell-type identity and capture subtle functional differences. These states arise from lineage-specific developmental Ca2+ programs that are detectable already in progenitor stages, and may precede differentiation into mature neuronal cell types. During neocortical development, many Ca2+ signaling genes, such as ADGRV1, NCALD, and CREB5, peak at distinct developmental stages, are evolutionarily conserved, and reflect transcriptional heterogeneity within progenitors associated with cell-fate decisions. Together, our findings provide an in-depth understanding of how a tightly regulated Ca2+ signaling transcriptome encodes cell-state-specific signaling programs and demonstrate that Ca2+ signaling is precisely tailored to distinct cell states.

Keywords: Biological sciences; Neuroscience; Transcriptomics

DOI: https://doi.org/10.1016/j.isci.2026.116055