{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:46:25Z","timestamp":1770270385306,"version":"3.49.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,4,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Translocase of inner membrane 50 (\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50) is a member of the translocase of inner membrane (\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              ) complex in the mitochondria. Previous research has demonstrated the role of\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 in the regulation of oxidative stress and cardiac morphology. However, the role of\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 in pathological cardiac hypertrophy remains unknown.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In the present study we found that the expression of\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 was downregulated in hypertrophic hearts. Using genetic loss\u2010of\u2010function animal models, we demonstrated that\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild\u2010type littermates. Moreover, we generated cardiomyocyte\u2010specific\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50. Meanwhile, expression of the\n              <jats:styled-content style=\"fixed-case\">ASK<\/jats:styled-content>\n              1\u2010\n              <jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>\n              \/P38 axis was increased in\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50\u2010deficient mice, and\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 overexpression decreased the activity of the\n              <jats:styled-content style=\"fixed-case\">ASK<\/jats:styled-content>\n              1\u2010\n              <jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>\n              \/P38 axis. Finally, we treated mice with the antioxidant N\u2010acetyl cysteine to reduce oxidative stress. After N\u2010acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 deficiency were all remarkably reversed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These data indicated that\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress.\n              <jats:styled-content style=\"fixed-case\">TIM<\/jats:styled-content>\n              50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure.\n            <\/jats:p>\n          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