BACKGROUND: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. METHODS: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3. RESULTS: HPV16-specific tumor-infiltrating T cells were present in 73.1% of HPV-associated oropharyngeal tumors. HPV16 specific CD8+ TILs were able to produce IFNγ upon specific stimulation and predominantly expressed PD-1 but not Tim-3. Specific IFNγ production was further enhanced after a blockade of both PD-1 and Tim-3 pathways but not after a PD-1 blockade alone. Additionally, the specific stimulation of anti-HPV16 CD8+ T cells suppressed Tim-3 upregulation after the PD-1 blockade. CONCLUSION: Our data provide the rationale for combination cancer immunotherapy approaches, including the dual blockade of PD-1 and Tim-3 and, potentially, the use of HPV16-directed therapeutic vaccines.

• Klíčová slova
• Human papillomavirus, Oropharyngeal cancer, PD-1, Tim-3, Tumor-infiltrating lymphocytes,
• MeSH
• antigeny CD279 antagonisté a inhibitory   metabolismus   MeSH
• buněčný receptor 2 viru hepatitidy A metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• cytokiny biosyntéza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 izolace a purifikace   MeSH
• nádory orofaryngu farmakoterapie   imunologie   metabolismus   virologie   MeSH
• nivolumab terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• senioři MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• únik nádoru z imunitní kontroly MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD279 MeSH
• buněčný receptor 2 viru hepatitidy A MeSH
• cytokiny MeSH
• HAVCR2 protein, human MeSH Prohlížeč
• nivolumab MeSH
• PDCD1 protein, human MeSH Prohlížeč
• protinádorové látky imunologicky aktivní MeSH

PURPOSE: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial. EXPERIMENTAL DESIGN: We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8+ T cells, CD20+ B cells, DC-LAMP+ dendritic cells as well as by PD-1+, CTLA4+, LAG-3+, and TIM-3+ cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach. RESULTS: High levels of PD-L1 and high densities of PD-1+ cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust TH1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1+TIM-3+CD8+ T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3+ cells improved patient stratification based on the intratumoral abundance of CD8+ T cells, the amount of PD-1+ cells failed to do so. CONCLUSIONS: Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively.

• MeSH
• antigen CTLA-4 imunologie   metabolismus   MeSH
• antigeny CD274 imunologie   metabolismus   MeSH
• buněčný receptor 2 viru hepatitidy A imunologie   metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom imunologie   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny asociované s lyzozomy imunologie   metabolismus   MeSH
• míra přežití MeSH
• nádorové biomarkery imunologie   metabolismus   MeSH
• nádorové proteiny imunologie   metabolismus   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• serózní cystadenokarcinom imunologie   metabolismus   patologie   MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• antigeny CD274 MeSH
• buněčný receptor 2 viru hepatitidy A MeSH
• CD274 protein, human MeSH Prohlížeč
• CTLA4 protein, human MeSH Prohlížeč
• HAVCR2 protein, human MeSH Prohlížeč
• LAMP3 protein, human MeSH Prohlížeč
• membránové glykoproteiny asociované s lyzozomy MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH

Depletion and functional impairment of circulating plasmacytoid dendritic cells (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of dysfunction of pDCs is unclear. Here, we studied the development of phenotype of pDCs in a cohort of HIV-1-infected individuals monitored before the initiation and during a 9-month follow up with antiretroviral therapy (ART). Using polychromatic flow cytometry, we detected significantly higher pDC-surface expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fcγ receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL, in treatment-naïve HIV-1-infected individuals before initiation of ART when compared to healthy donors. After 9 months of ART, all of these markers approached but did not reach the expression levels observed in healthy donors. We found that the rate of decline in HIV-1 RNA level over the first 3 months of ART negatively correlated with the expression of TIM-3 on pDCs. We conclude that immunogenic phenotype of pDCs is not significantly restored after sustained suppression of HIV-1 RNA level in ART-treated patients and that the level of the TIM-3 expressed on pDCs in treatment naïve patients could be a predictive marker of the rate of decline in the HIV-1 RNA level during ART.

• Klíčová slova
• BDCA-2, HIV-1, T cell Ig and mucin-domain containing molecule 3 (TIM-3), Toll-like receptors 7 and 9 (TLR7/9), antiretroviral therapy (ART), innate and adaptive immune responses, pDC dysfunction, plasmacytoid dendritic cells (pDCs),
• MeSH
• biologické markery MeSH
• buněčný receptor 2 viru hepatitidy A genetika   MeSH
• CD4-pozitivní T-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• dospělí MeSH
• exprese genu * MeSH
• HIV infekce farmakoterapie   genetika   imunologie   virologie   MeSH
• HIV-1 * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• počet CD4 lymfocytů MeSH
• RNA virová MeSH
• virová nálož MeSH
• vysoce aktivní antiretrovirová terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• buněčný receptor 2 viru hepatitidy A MeSH
• HAVCR2 protein, human MeSH Prohlížeč
• RNA virová MeSH

Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8+ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in patients with AML. Natural killer (NK) cells are central players in AML-targeting immune responses. However, little is known on the relationship between co-inhibitory receptors expressed by NK cells and the ability of the latter to control AML. Here, we show that hepatitis A virus cellular receptor 2 (HAVCR2, best known as TIM-3) is highly expressed by NK cells from AML patients, correlating with improved functional licensing and superior effector functions. Altogether, our data indicate that NK cell frequency as well as TIM-3 expression levels constitute prognostically relevant biomarkers of active immunity against AML.

• Klíčová slova
• Co-inhibitory receptor, innate lymphoid cells, lag-3, tigit, vista,
• MeSH
• akutní myeloidní leukemie * farmakoterapie   MeSH
• buněčný receptor 2 viru hepatitidy A * MeSH
• buňky NK * MeSH
• CD8-pozitivní T-lymfocyty MeSH
• cytotoxické T-lymfocyty MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• buněčný receptor 2 viru hepatitidy A * MeSH
• HAVCR2 protein, human MeSH Prohlížeč

The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.

• Klíčová slova
• AML, DNMT3A, NPM1, TIM-3, immunophenotype,
• MeSH
• akutní myeloidní leukemie * diagnóza   genetika   MeSH
• antigeny CD274 genetika   MeSH
• biologické markery MeSH
• buněčný receptor 2 viru hepatitidy A genetika   MeSH
• DNA methyltransferasa 3A * genetika   MeSH
• lidé MeSH
• mutace MeSH
• nukleofosmin * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD274 MeSH
• biologické markery MeSH
• buněčný receptor 2 viru hepatitidy A MeSH
• DNA methyltransferasa 3A * MeSH
• DNMT3A protein, human MeSH Prohlížeč
• NPM1 protein, human MeSH Prohlížeč
• nukleofosmin * MeSH

Translocase of outer mitochondrial membrane 34 (TOMM34) orchestrates heat shock protein 70 (HSP70)/HSP90-mediated transport of mitochondrial precursor proteins. Here, using in vitro phosphorylation and refolding assays, analytical size-exclusion chromatography, and hydrogen/deuterium exchange MS, we found that TOMM34 associates with 14-3-3 proteins after its phosphorylation by protein kinase A (PKA). PKA preferentially targeted two serine residues in TOMM34: Ser93 and Ser160, located in the tetratricopeptide repeat 1 (TPR1) domain and the interdomain linker, respectively. Both of these residues were necessary for efficient 14-3-3 protein binding. We determined that phosphorylation-induced structural changes in TOMM34 are further augmented by binding to 14-3-3, leading to destabilization of TOMM34's secondary structure. We also observed that this interaction with 14-3-3 occludes the TOMM34 interaction interface with ATP-bound HSP70 dimers, which leaves them intact and thereby eliminates an inhibitory effect of TOMM34 on HSP70-mediated refolding in vitro In contrast, we noted that TOMM34 in complex with 14-3-3 could bind HSP90. Both TOMM34 and 14-3-3 participated in cytosolic precursor protein transport mediated by the coordinated activities of HSP70 and HSP90. Our results provide important insights into how PKA-mediated phosphorylation and 14-3-3 binding regulate the availability of TOMM34 for its interaction with HSP70.

• Klíčová slova
• 14-3-3 protein, 70-kDa heat shock protein (Hsp70), HSP70, Hsp70, Tomm34, dimerization, hydrogen-deuterium exchange, molecular chaperone, phosphorylation, protein folding, protein import, protein kinase A (PKA), protein-nucleic acid interaction, protein–protein interaction, translocase of outer mitochondrial membrane 34 (TOMM34),
• MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fosforylace fyziologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• mitochondriální importní komplex MeSH
• mitochondriální membrány metabolismus   MeSH
• mitochondriální proteiny metabolismus   MeSH
• molekulární chaperony metabolismus   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• proteiny 14-3-3 metabolismus   MeSH
• proteiny tepelného šoku HSP70 metabolismus   MeSH
• proteiny tepelného šoku HSP72 metabolismus   MeSH
• proteiny tepelného šoku HSP90 metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktory genetika   metabolismus   MeSH
• transportní proteiny mitochondriální membrány genetika   metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BCL2-associated athanogene 1 protein MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• mitochondriální importní komplex MeSH
• mitochondriální proteiny MeSH
• molekulární chaperony MeSH
• proteinkinasy závislé na cyklickém AMP MeSH
• proteiny 14-3-3 MeSH
• proteiny tepelného šoku HSP70 MeSH
• proteiny tepelného šoku HSP72 MeSH
• proteiny tepelného šoku HSP90 MeSH
• TOMM34 protein, human MeSH Prohlížeč
• transkripční faktory MeSH
• transportní proteiny mitochondriální membrány MeSH

The mitochondrial protein import machinery of trypanosomatids is highly divergent from that of the well-studied models such as baker's yeast. A notable example is that the central catalyst of the mitochondrial intermembrane space import and assembly pathway (MIA), named Mia40, is missing in trypanosomatids. Mia40 works in a two-step process. First it recognizes by direct binding reduced MIA substrate proteins and then catalyzes their oxidative folding to produce intramolecular disulfide bridges. It was recently proposed that a thioredoxin-like subunit of the trypanosomal mitochondrial contact site and cristae organizing system (MICOS) called TbMic20 may be the Mia40 replacement. Our study performed on procyclic stage of the parasite revealed that each of the two cysteines in TbMic20's active site is essential for the stability of MIA substrate proteins although they do not form a disulfide bridge in vivo. The two cysteines of Mia40's active site form an intramolecular disulfide bridge at steady state, which is a prerequisite for its oxidative folding of MIA substrates. Thus, we conclude that TbMic20 is unlikely to represent a bona fide Mia40 replacement and plays a still unresolved role in the stability and/or import of MIA substrates in trypanosomatids. Despite this, the effect of TbMic20 depletion and mutation indicates that the trypanosomal MICOS complex still plays a vital role in the maturation and/or stability of proteins imported by the MIA pathway.

• Klíčová slova
• Intermembrane space, MICOS, Mitochondrion, Oxidative folding, Protein import, Trypanosoma,
• MeSH
• chlorprofam metabolismus   MeSH
• cystein metabolismus   MeSH
• disulfidy MeSH
• mitochondriální importní komplex MeSH
• mitochondriální proteiny metabolismus   MeSH
• oxidace-redukce MeSH
• Saccharomyces cerevisiae - proteiny * genetika   MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• sbalování proteinů MeSH
• thioredoxiny genetika   metabolismus   MeSH
• transport proteinů MeSH
• transportní proteiny mitochondriální membrány genetika   MeSH
• transportní proteiny metabolismus   MeSH
• Trypanosoma brucei brucei * genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorprofam MeSH
• cystein MeSH
• disulfidy MeSH
• MIA40 protein, S cerevisiae MeSH Prohlížeč
• mitochondriální importní komplex MeSH
• mitochondriální proteiny MeSH
• Saccharomyces cerevisiae - proteiny * MeSH
• thioredoxiny MeSH
• transportní proteiny mitochondriální membrány MeSH
• transportní proteiny MeSH

CD8+ T cells protect against tumors and intracellular pathogens. The inflammatory cytokines IL-2, IL-15, and IL-7 are necessary for their expansion. However, elevated serum levels of these cytokines are often associated with cancer, poorer prognosis of cancer patients, and exhaustion of antigen-expanded CD8+ T cells. The impact of acute conditioning of antigen-expanded CD8+ T cells with these cytokines is unknown. Here, we generated antigen-expanded CD8+ T cells using dendritic cells and PC-3 cells. The cells were acutely (18-24 h) conditioned with IL-2 and either the GSK3β inhibitor TWS119, the mTORC1 inhibitor rapamycin, or the mTORC1/2 inhibitor Torin1, then their immediate and post-re-expansion (distal) cytokine responses after antigen rechallenge were evaluated. We found that acute IL-2 conditioning upregulated the immediate antigen-induced cytokine response of the tested cells. Following their re-expansion, however, the cells showed a decreased cytokine response. These IL-2 conditioning-mediated impacts were counteracted with TWS119 or rapamycin but not with Torin1. Our data revealed that the acute conditioning of antigen-expanded CD8+ T cells with IL-2 modulates the GSK3β-mTORC signaling axis. This modulation differentially affected the immediate and distal cytokine responses of the cells. The acute targeting of this signaling axis could, therefore, represent a novel strategy for the modulation of antigen-expanded CD8+ T cells.

• Klíčová slova
• CD8+ T cells, GSK-3β, TWS119, Tim-3, Torin1, antigen rechallenge, cytokine starvation, mTOR, rapamycin,
• Publikační typ
• časopisecké články MeSH

Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of Cox-2 mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.

• Klíčová slova
• CD8+ T lymphocytes, Cox-2, cyclooxygenase 2, HNSCC, HNSCC, head and neck squamous cell carcinoma, HPV, HPV, human papillomavirus, PD-1, PD-1, programmed cell death 1, PD-L1, programmed cell death-ligand 1, Tim-3, Tim-3, T cell immunoglobulin and mucin protein 3, Treg, regulatory T cell, mDC, myeloid dendritic cell, pDC, plasmacytoic dendritic cell,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (>48h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity.

• Klíčová slova
• Doxorubicin, Ethidium Bromide, Mitochondrial DNA stress, Mitochondrial transcription factor A, Nucleoid clusters,
• MeSH
• buňky Hep G2 MeSH
• DNA vazebné proteiny metabolismus   MeSH
• doxorubicin MeSH
• dynaminy MeSH
• ethidium MeSH
• GTP-fosfohydrolasy metabolismus   MeSH
• jaterní mitochondrie metabolismus   MeSH
• lidé MeSH
• mitochondriální DNA metabolismus   MeSH
• mitochondriální importní komplex MeSH
• mitochondriální proteiny metabolismus   MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• poškození DNA MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• transkripční faktory metabolismus   MeSH
• transportní proteiny mitochondriální membrány metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• DNM1L protein, human MeSH Prohlížeč
• doxorubicin MeSH
• dynaminy MeSH
• ethidium MeSH
• GTP-fosfohydrolasy MeSH
• MAP1LC3B protein, human MeSH Prohlížeč
• mitochondriální DNA MeSH
• mitochondriální importní komplex MeSH
• mitochondriální proteiny MeSH
• NABP2 protein, human MeSH Prohlížeč
• nádorový supresorový protein p53 MeSH
• proteiny asociované s mikrotubuly MeSH
• TFAM protein, human MeSH Prohlížeč
• TIMM23 protein, human MeSH Prohlížeč
• transkripční faktory MeSH
• transportní proteiny mitochondriální membrány MeSH