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| Title | Cryoelectron tomography reveals an age-related decline in mitoribosomes that contributes to T cell dysfunction in older individuals. |
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| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 123, Issue 31, Page e2608102123, Year 2026 |
| Publish date | Aug 4, 2026 |
 Authors | Jingwen Chen / Lili Su / Bangze Pan / Junhao Sang / Linlin Li / Junsong Huang / Zhao-Lan Hu / Lixin Wang / Xiaojie Zhang / Jun Jin /  |
| PubMed Abstract | Mitochondrial dysfunction drives T cell aging in mice. Yet, due to fundamental differences in T cell aging mechanisms between species, whether human T cells exhibit similar mitochondrial alterations ...Mitochondrial dysfunction drives T cell aging in mice. Yet, due to fundamental differences in T cell aging mechanisms between species, whether human T cells exhibit similar mitochondrial alterations remains unclear, with existing evidence often conflicting. Using cryoelectron tomography, we resolved the structure and spatial organization of mitochondrial ribosomes in primary human CD8 T cells under physiological conditions. Comparative analysis with human aging models revealed an age-related reduction in mitoribosome abundance and in higher-order mitoribosome organization, which is necessary for cooperative translation. Defective mitochondrial translation suppressed cytosolic ribosomal protein expression, thereby limiting mitochondrial biogenesis. The consequent reduction in mitochondrial mass induced an aged T cell phenotype characterized by compromised memory phenotypes and proliferative capacity. Enhancing mitochondrial translation via overexpression of the mitoribosomal component Mrps5 reversed aged T cell phenotypes in a mouse model of viral infection or tumor. Together, our findings provide nanoscale-resolution views of internal mitochondrial structures in situ, revealing an age-related loss of mitoribosomes. This loss contributes to mitochondrial dysfunction and the subsequent decline in T cell function observed in older individuals. Restoring mitochondrial translation may therefore represent a strategy for mitigating T cell dysfunction in the aging population. |
 External links | Proc Natl Acad Sci U S A / PubMed:42525521 |
| Methods | EM (subtomogram averaging) / EM (tomography) |
| Resolution | 16.0 - 31.0 Å |
| Structure data |  EMDB-69516: In-cell map of mitoribosome from T cells of middle-aged patients after restimulation by subtomogram averaging  EMDB-69519: Tomogram of mitochondria in T cell from middle-aged patients after restimulation  EMDB-69521: Tomogram of mitochondria in T cell from older patients after restimulation  EMDB-69523: In-cell map of mitoribosome from T cells of older patients after restimulation by subtomogram averaging  EMDB-69526: In-cell map of electron transport chain supercomplex from T cells of middle-aged patients after restimulation by subtomogram averaging  EMDB-69528: In-cell map of electron transport chain supercomplex from T cells of older patients after restimulation by subtomogram averaging |
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Homo sapiens (human)