{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:39:21Z","timestamp":1787063961377,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The induction of mitochondrial quality control (MQC) mechanisms is essential for the re\u2010establishment of mitochondrial homeostasis and cellular bioenergetics during periods of stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role and regulatory mechanisms in alcoholic cardiomyopathy (ACM) remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We explored whether two mitochondria\u2010related proteins, phosphoglycerate mutase 5 (Pgam5) and prohibitin 2 (Phb2), influence MQC in male mice during ACM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Myocardial Pgam5 expression was upregulated in a male mouse model of ACM. Notably, following ACM induction, heart dysfunction was markedly reversed in male cardiomyocyte\u2010specific\n                      <jats:italic>Pgam5<\/jats:italic>\n                      knockout (\n                      <jats:italic>\n                        Pgam5\n                        <jats:sup>cKO<\/jats:sup>\n                      <\/jats:italic>\n                      ) mice. Meanwhile, in alcohol\u2010treated male mouse\u2010derived neonatal cardiomyocytes,\n                      <jats:italic>Pgam5<\/jats:italic>\n                      depletion preserved cell survival and restored mitochondrial dynamics, mitophagy, mitochondrial biogenesis and the mitochondrial unfolded protein response (mtUPR). We further found that in alcohol\u2010treated cardiomyocyte, Pgam5 binds Phb2 and induces its dephosphorylation at Ser91. Alternative transduction of phospho\u2010mimetic (Phb2\n                      <jats:sup>S91D<\/jats:sup>\n                      ) and phospho\u2010defective (Phb2\n                      <jats:sup>S9A<\/jats:sup>\n                      ) Phb2 mutants attenuated and enhanced, respectively, alcohol\u2010related mitochondrial dysfunction in cardiomyocytes. Moreover, transgenic male mice expressing\n                      <jats:italic>\n                        Phb2\n                        <jats:sup>S91D<\/jats:sup>\n                      <\/jats:italic>\n                      were resistant to alcohol\u2010induced heart dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We conclude that ACM\u2010induced Pgam5 upregulation results in Pgam5\u2010dependent Phb2\n                      <jats:sup>S91<\/jats:sup>\n                      dephosphorylation, leading to MQC destabilisation and mitochondrial dysfunction in heart. Therefore, modulating the Pgam5\/Phb2 interaction could potentially offer a novel therapeutic strategy for ACM in male mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Pgam5<\/jats:italic>\n                            knockout attenuates alcohol\u2010induced cardiac histopathology and heart dysfunction in male mice.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Pgam5<\/jats:italic>\n                            KO reduces alcohol\u2010induced myocardial inflammation, lipid peroxidation and metabolic dysfunction in male mice.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pgam5 depletion protects mitochondrial function in alcohol\u2010exposed male mouse cardiomyocytes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pgam5 depletion normalises MQC in ACM.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>EtOH impairs MQC through inducing Phb2 dephosphorylation at Ser91.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pgam5 interacts with Phb2 and induces Phb2 dephosphorylation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Transgenic mice expressing a Ser91 phospho\u2010mimetic Phb2 mutant are resistant to ACM.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.1806","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T01:39:23Z","timestamp":1723685963000},"source":"Crossref","is-referenced-by-count":13,"title":["Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin\u20102 dephosphorylation and impairing mitochondrial quality control"],"prefix":"10.1002","volume":"14","author":[{"given":"Jun","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery 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