The schematics of immunomodulatory metabolites roles in shaping the inflammatory response of the macrophage. (A) The immunoregulatory functions of metabolites in macrophages upon pro-inflammatory stimulation (e.g., LPS/IFN-γ). LPS, lipopolysaccharide; IFN-γ, interferon-γ; NF-κB, nuclear factor-κB; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; IL-1β, interleukin-1β; PHD, prolyl hydroxylase; HIF-1α, hypoxia-inducible factor-1α; SDH, succinate dehydrogenase; IDH, isocitrate dehydrogenase; IRG1, immune-responsive gene 1; ACLY, ATP-citrate Lyase; PGE2, prostaglandin 2; H3K4me3, histone 3 lysine 4 tri-methylation; H3K27Ac, histone 3 lysine 27 acetylation; SUCNR1, succinate receptor 1; TFEB, transcription factor EB; Keap1, kelch-like ECH-associated protein 1; Nrf2, nuclear factor erythroid 2-related factor 2; ATF3, activating transcription factor 3; Rab32/BLOC3, Rab32/member RAS oncogene family 32/biogenesis of lysosomal organelles complex 1 subunit 3. (B) The immunoregulatory functions of metabolites in macrophages upon anti-inflammatory stimulation (e.g., IL-4/IL-13). IL-4, interleukin-4; IL-13, interleukin-13; FAO, fatty acid oxidation; PPAR-γ, peroxisome proliferator activated receptor-gamma; UDP-GluNAc, uridine diphosphate N-acetylglucosamine; ChREBP, carbohydrate response element binding protein; NADPH/NADP, nicotinamide-adenine dinucleotide phosphate reduced/nicotinamide-adenine dinucleotide phosphate oxidized; GPCR/PLC, G protein-coupled receptor/phospholipase C; H3K27me2, histone 3 lysine 4 di-methylation; JAK1/STAT6, janus kinase 1/Signal transducer and activator of transcription 6; ARG1, arginase 1; FIZZ1, found in inflammatory zone 1; MRC1, mannose receptor C-type 1. The red and blue color-coded components within the figures respectively represent the constituents of anti- and pro-inflammatory responses.

Overall architecture of Fungal MCU of N.crassa (37). (A) Each domains of N.crassa MCU are indicated (PDB code: 6DT0). Each protomer are colored separately. Missing part of N.crassa MCU structure are presented by black dashes. (B) Top view of N.crassa MCU structure. Ca²⁺ are represented by red spheres. Each TMH is marked in red letters at single protomer. (C) Bottom view of N.crassa MCU structure.

Alignment of SUMO protein sequences and SUMO pathway diagram. (A) Sequence alignment of human SUMO-1 through SUMO-5 with yeast SUMO (Smt3) using Molecular Evolutionary Genetic Analysis software (MEGA, https://www.megasoftware.net/). Different letters and colors indicate different amino acids, and asterisks denote amino acids conserved among all SUMO proteins. (B) Diagram of the SUMOylation cycle. The precursor form of SUMO is processed by SENP proteases to create a mature form with a C-terminal Gly-Gly (GG) motif. Mature SUMO is ATP-dependent and activated by heterodimeric E1 SUMO-activating enzymes, SAE1 and SAE2, through a catalytic cysteine (C) residue in SAE2. Next, SUMO is transferred to the C residue of the E2 SUMO-conjugating enzyme (Ubc9), resulting in the conjugation of SUMO to the lysine (K) residues of the substrate protein with the aid of an E3 SUMO ligase. Finally, SENPs can deconjugate SUMO from the substrate or edit SUMO chains, after which SUMO is recycled through the conjugation event.