MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure, and maintenance of oligomeric ATP synthase. My results provide insight into how MCL-1's surprisingly diverse salutary functions may control the survival of both normal and cancer cells.
","abstract_html":"<p>MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure, and maintenance of oligomeric ATP synthase. My results provide insight into how MCL-1's surprisingly diverse salutary functions may control the survival of both normal and cancer cells. </p>","abstract_has_math":false,"creators":["Perciavalle, Rhonda"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Joseph T. Opferman, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-12-01T08:00:00Z","date_published":"2012-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:17Z","subjects":["Apoptosis","Cancer","Cell Death","MCL-1","Metabolism","Mitochondria","Medical Genetics","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/203","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Joseph T. Opferman, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Perciavalle, Rhonda"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Apoptosis","Cancer","Cell Death","MCL-1","Metabolism","Mitochondria","Medical Genetics","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/203"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure, and maintenance of oligomeric ATP synthase. My results provide insight into how MCL-1's surprisingly diverse salutary functions may control the survival of both normal and cancer cells.
"]},{"key":"dc:title","label":"Title","values":["Anti-apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration"]}]}],"canonical_facts":{"dc:contributor":["Joseph T. Opferman, Ph.D."],"dc:creator":["Perciavalle, Rhonda"],"dc:date.available":["2016-06-09T07:00:00Z"],"dc:description.abstract":["MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to facilitate normal mitochondrial fusion, ATP production, membrane potential, respiration, cristae ultrastructure, and maintenance of oligomeric ATP synthase. My results provide insight into how MCL-1's surprisingly diverse salutary functions may control the survival of both normal and cancer cells.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/203"],"dc:subject":["Apoptosis","Cancer","Cell Death","MCL-1","Metabolism","Mitochondria","Medical Genetics","Medical Sciences","Medicine and Health Sciences"],"dc:title":["Anti-apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:17Z"}