Journal: The Journal of Biological Chemistry

Article Title: Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives

doi: 10.1016/j.jbc.2026.111455

Figure Lengend Snippet: Integrated Stress-Responsive Regulation of Mitochondrial Translation and Cellular Homeostas is. A , Mito-Nuclear Crosstalk: Mitochondrial dysfunction marked by translation defects, oxidative stress, and ATP depletion activates retrograde signaling to the nucleus through ATF4. This triggers the transcription of key nuclear regulators (including NRF1, NRF2, POLRMT, TFAM) facilitating mitochondrial biogenesis and recovery. Transcriptional coactivators PGC-1α amplify this response. B , Integrated Stress Response (ISR): Stress sensors (PERK, GCN2, HRI) phosphorylate eIF2α, initiating the Integrated Stress Response (ISR), which globally attenuates translation while promoting selective synthesis of stress regulators like ATF4 and CHOP. The DELE1-OMA1-HRI axis further links mitochondrial dysfunction to cytosolic ISR signaling. C , Metabolic Reprogramming: In immune and proliferating cells, mitochondrial metabolism adapts by shifting between glycolysis and OXPHOS. These shifts are mediated by changes in mitochondrial translation that adjusts the TCA cycle and respiratory chain activity. Mitochondrial transcription and translation are upregulated in response to cellular energy demands, supporting immune cell functions and tissue homeostasis. mTORC1, sensing amino acids, oxygen, and energy status, regulates translation through effectors like S6K1, 4E-BP1/2, and eIF4B, thereby integrating growth signals with mitochondrial function. This axis governs anabolic responses and mitochondrial translation during growth, cellular stress and immune activation. D , Mitochondrial unfolded protein response (mtUPR): The mitochondrial unfolded protein response (mtUPR) is activated upon accumulation of misfolded proteins in the mitochondrial matrix. Proteases such as LONP1 and CLPP, along with chaperones HSP60, HSP70, and HSP10, maintain mitochondrial proteostasis by promoting correct protein folding and degrading damaged proteins. This ensures the integrity of respiratory chain components and modulates cytosolic translation. Under mitochondrial stress, defective import of nuclear-encoded mitochondrial proteins leads to their ubiquitination and proteasomal degradation, safeguarding cytosolic protein homeostasis and preventing proteotoxicity. E , RNA-binding proteins: RNA-binding proteins (RBPs) such as LRPPRC, TACO1, and CLUH play critical roles in post-transcriptional regulation of mtDNA. LRPPRC stabilizes mitochondrial mRNAs and promotes their polyadenylation and translation, whereas TACO is a mitochondrial translational activator specifically required for efficient translation of mitochondrial encoded COX1 (cytochrome c oxidase subunit I). CLUH binds to nuclear-encoded mitochondrial mRNAs in the cytoplasm and regulates their stability, localization, and translation, contributing to proper mitochondrial biogenesis.

Article Snippet: LONP1 , Proteostasis, degradation of unfolded and oxidatively damaged Proteins , Cerebral, ocular, dental, auricular and skeletal anomalies (CODAS) Syndrome ( ) .

Techniques: Activity Assay, Activation Assay, Ubiquitin Proteomics, RNA Binding Assay

Journal: Frontiers in Cell and Developmental Biology

Article Title: Beyond the genome: clinical challenges in diagnosing LONP1 -related mitochondrial disorders

doi: 10.3389/fcell.2026.1779332

Figure Lengend Snippet: The protein structure of LONP1. (A) The red arrow points to the position of Arg301 in the LONP1 protein model. (B) Stick models show the amino acids around Arg301; four hydrogen bonds are formed among the four residues (Val297, Lys298, Ile304, and Ala305) surrounding Arg301. (C) Stick models show the amino acids around Trp301; four hydrogen bonds are formed among the four residues (Val297, Lys298, Ile304, and Ala305) surrounding Trp301.

Article Snippet: Human protein atlas information ( ) shows that LONP1 mRNA is expressed at high levels in the adrenal gland.

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: Beyond the genome: clinical challenges in diagnosing LONP1 -related mitochondrial disorders

doi: 10.3389/fcell.2026.1779332

Figure Lengend Snippet: (A) The pedigree of the family: The outcome of the first pregnancy was spontaneous abortion. Born from the second pregnancy, the proband was the first live-born child of the parents and presented with recurrent seizures, microcephaly, pachygyria, developmental delay, hyperlactatemia, and hypoadrenocorticism. (B) Sanger sequence chromatogram of LONP1 . Sanger sequencing showed that c.901C>T (p.Arg301Trp) was heterozygous in the proband, and the variant was not detected in the parents.

Article Snippet: Human protein atlas information ( ) shows that LONP1 mRNA is expressed at high levels in the adrenal gland.

Techniques: Sequencing, Variant Assay

Journal: Frontiers in Cell and Developmental Biology

Article Title: Beyond the genome: clinical challenges in diagnosing LONP1 -related mitochondrial disorders

doi: 10.3389/fcell.2026.1779332

Figure Lengend Snippet: Schematic of LONP1 and the localization of the variants of LONP1 identified in previous reports and in this study. Variants above the axis exhibit an AD inheritance pattern, whereas those below the axis exhibit an AR inheritance pattern. The red circles correspond to NDD cases, the green diamonds to CODAS syndrome cases, and the blue squares to cataract cases. The numerical values following the * represent the reported cases with the same variants.

Article Snippet: Human protein atlas information ( ) shows that LONP1 mRNA is expressed at high levels in the adrenal gland.

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: Beyond the genome: clinical challenges in diagnosing LONP1 -related mitochondrial disorders

doi: 10.3389/fcell.2026.1779332

Figure Lengend Snippet: Clinical feature distribution of LONP1-related diseases across different subgroups.

Article Snippet: Human protein atlas information ( ) shows that LONP1 mRNA is expressed at high levels in the adrenal gland.

Techniques:

Journal: Molecular Medicine

Article Title: Complement protein C1q induces endothelial apoptosis through C1qBP regulation of mitochondrial function in lung endothelial cells in systemic sclerosis

doi: 10.1186/s10020-026-01445-0

Figure Lengend Snippet: C1qBP affected PHB2 phosphorylation and cytoplasmic translocation as well as mitochondrial dysfunction in endothelial cells. BLM-induced endothelial cells were treated with si-C1qBP. A - B Western blot analysis was utilized to examine the effects of si-C1qBP on C1qBP levels and the phosphorylation and cytoplasmic translocation of PHB2. C - D The binding and co-localization of C1qBP with PHB2 were observed through co-immunoprecipitation and immunofluorescence. E - F Western blot was performed to evaluate the impact of C1qBP on the expression of apoptosis-related proteins (BAX and Bcl-2), mitophagy-related proteins (Beclin1, Parkin, Pink1), as well as UPRmt-related markers (mtDnaJ, ClpP, LonP1, Hsp10). G Red CMXRos staining was used to assess the effect of C1qBP on mitochondrial activity in endothelial cells. H The influence of C1qBP on intracellular Ca 2+ levels in endothelial cells was measured by Fluo-4 AM fluorescent probe detection. I - J MMP detection was conducted to observe the effect of C1qBP on the MMP of endothelial cells. K - L The impact of C1qBP on ATP levels and electron transport chain (complexes I-IV) activity in endothelial cells was determined by ATP colorimetric/fluorescence assay and mitochondrial electron transport chain activity detection. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. Con/ BLM + si-NC

Article Snippet: Antibodies used included: C1qA Primary Antibody (1:1,000, A1821, Abclonal), C1qB Primary Antibody (1:1,000, BD-PB4657, Biodragon), C1qBP Primary Antibody (1:1,000, 68084-1-Ig, Proteintech), COV IV Primary Antibody (1:1, 000, 4850 S, Cellular), PHB2 primary antibody (1:1,000, 66424-1-Ig, Proteintech), Cleaved caspase-3 primary antibody (1:1,000, 68773-1-Ig, Proteintech), ICAM1 primary antibody (1:1,000, A20472, Abclonal), ZO1 primary antibody (1:1,000, 21773-1-AP, Proteintech), ZO2 primary antibody (1:1,000, 18900-1-AP, Proteintech), OCLN primary antibody (1:1,000, 27260-1-AP, Proteintech), JAM3 primary antibody (1:1,000, BD-PN0240, Biodragon), BAX primary antibody (1:1,000, CY5059, Abways), Bcl-2 primary antibody (1:1,000, ab182858, Abcam), Beclin1 primary antibody (1:1,000, 3738 S, Cell signalling), Parkin primary antibody (1:1,000, CY6641, Abways), Pink1 primary antibody (1:1,000, BY0130, Abways), ClpP primary antibody (1:1,000, ab124822, Abcam), mtDnaJ primary antibody (1:1,000, ab124822, Abcam), LonP1 primary antibody (1:1,000, A03808-2, BOSTER), Hsp10 primary antibody (1:1,000, CY8473, Abways), and β-actin primary antibody (1:1,000, 66009-1-Ig, Proteintech).

Techniques: Phospho-proteomics, Translocation Assay, Western Blot, Binding Assay, Immunoprecipitation, Immunofluorescence, Expressing, Staining, Activity Assay, Fluorescence

Journal: Molecular Medicine

Article Title: Complement protein C1q induces endothelial apoptosis through C1qBP regulation of mitochondrial function in lung endothelial cells in systemic sclerosis

doi: 10.1186/s10020-026-01445-0

Figure Lengend Snippet: C1qBP promoted endothelial cell apoptosis by causing mitochondrial dysfunction through affecting the cytosolic translocation of PHB2. A PHB2-S293A phosphorylation-deficient mutant was constructed. BLM-induced endothelial cells were co-transfected with PHB2-S293A (WT or MUT) and siRNA (si-NC or si-C1qBP), respectively. A Western blot analysis of C1qBP, PHB2 and p-PHB2 expression. B Western blot analysis of apoptosis- and mitophagy-related proteins BAX, Bcl-2, Beclin1, Parkin, and Pink1. C - D Immunofluorescence detection of BAX, Bcl-2, Beclin1, Parkin and Pink1 expression. E Western blot analysis of mitochondrial unfolded protein response (UPRmt)-related markers mtDnaJ, ClpP, LonP1 and Hsp10. F Red CMXRos staining to detect mitochondrial activity. G Fluo-4 AM fluorescent probe to measure intracellular Ca 2+ levels. H Evaluation of mitochondrial electron transport chain (ETC) activity. I JC-1 assay to detect mitochondrial membrane potential (MMP). J ATP colorimetric/fluorometric assay kit to measure ATP levels. K Flow cytometry analysis of the number of viable endothelial cells. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. BLM + si-NC+PHB2-S293A WT/ BLM + si-C1qBP+PHB2-S293A WT/ BLM + si-NC+PHB2-S293A MUT. ns means no significant difference vs. BLM + si-NC+PHB2-S293A WT/ BLM + si-C1qBP+PHB2-S293A WT

Article Snippet: Antibodies used included: C1qA Primary Antibody (1:1,000, A1821, Abclonal), C1qB Primary Antibody (1:1,000, BD-PB4657, Biodragon), C1qBP Primary Antibody (1:1,000, 68084-1-Ig, Proteintech), COV IV Primary Antibody (1:1, 000, 4850 S, Cellular), PHB2 primary antibody (1:1,000, 66424-1-Ig, Proteintech), Cleaved caspase-3 primary antibody (1:1,000, 68773-1-Ig, Proteintech), ICAM1 primary antibody (1:1,000, A20472, Abclonal), ZO1 primary antibody (1:1,000, 21773-1-AP, Proteintech), ZO2 primary antibody (1:1,000, 18900-1-AP, Proteintech), OCLN primary antibody (1:1,000, 27260-1-AP, Proteintech), JAM3 primary antibody (1:1,000, BD-PN0240, Biodragon), BAX primary antibody (1:1,000, CY5059, Abways), Bcl-2 primary antibody (1:1,000, ab182858, Abcam), Beclin1 primary antibody (1:1,000, 3738 S, Cell signalling), Parkin primary antibody (1:1,000, CY6641, Abways), Pink1 primary antibody (1:1,000, BY0130, Abways), ClpP primary antibody (1:1,000, ab124822, Abcam), mtDnaJ primary antibody (1:1,000, ab124822, Abcam), LonP1 primary antibody (1:1,000, A03808-2, BOSTER), Hsp10 primary antibody (1:1,000, CY8473, Abways), and β-actin primary antibody (1:1,000, 66009-1-Ig, Proteintech).

Techniques: Translocation Assay, Phospho-proteomics, Mutagenesis, Construct, Transfection, Western Blot, Expressing, Immunofluorescence, Staining, Activity Assay, Membrane, ATP Colorimetric Fluorometric Assay, Flow Cytometry