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Nutrient Stress Induced Lipid Metabolism: Exploring the SIRT2-ACSS2 Intersection
Nutrient Stress Induced Lipid Metabolism: Exploring the SIRT2-ACSS2 Intersection
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152032
- ISBN
- 9798384049166
- DDC
- 574
- 저자명
- Karim, Rezwana.
- 서명/저자
- Nutrient Stress Induced Lipid Metabolism: Exploring the SIRT2-ACSS2 Intersection
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 108 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Lin, Hening.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약Mammalian cells possess intricate mechanisms to adapt to malnutrition and starvation, with de novo lipogenesis (DNL) emerging as a pivotal pathway during stress. This thesis explores the regulation of lipid metabolism under nutrient stress, focusing on the interplay between Sirtuin 2 (SIRT2) and Acetyl-CoA Synthetase 2 (ACSS2).In Chapter 1, I provide an overview of acetyl-CoA's role in lipogenesis, highlighting its various sources and use in fatty acid synthesis and histone acetylation. Specifically, I explore the regulatory roles of ACSS2 and SIRT2 in lipogenesis, laying the foundation for understanding how cells manage nutrient stress, particularly amino acid deficiency.Chapter 2 explores how SIRT2, ACSS2, and lipid metabolism interact during times of nutrient stress, particularly amino acid deficiency We reveal a novel mechanism wherein SIRT2 catalyzes the deacetylation of ACSS2 at lysine residue K271, resulting in ubiquitination and degradation of ACSS2 by the proteasome. Substitution of K271 leads to reduced ubiquitination of ACSS2, higher levels of ACSS2 protein, and enhanced lipogenesis, revealing a cellular mechanism for the efficient regulation of lipogenesis under nutrient stress.In Chapter 3, we establish a nuclear role for the SIRT2-ACSS2 axis. Through qPCR analysis and functional assays, our study demonstrates that SIRT2 knockdown elevates the expression of key lipogenic genes, Fatty Acid Synthase (FASN) and Acetyl-CoA Carboxylase Alpha (ACACA). Moreover, inhibition of ACSS2 attenuates the upregulation of FASN induced by SIRT2 depletion, indicating a functional link between SIRT2, ACSS2, and FASN expression. These results are important in the field of cancer biology, as changes in FASN expression due to acetate supplementation closely resemble those caused by SIRT2 modulation in different cancer cell types.
- 일반주제명
- Biochemistry
- 일반주제명
- Cellular biology
- 일반주제명
- Biology
- 일반주제명
- Molecular biology
- 키워드
- Nutrient stress
- 키워드
- Lipid metabolism
- 키워드
- Mammalian cells
- 기타저자
- Cornell University Biochemistry Molecular and Cell Biology
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798384049166
■035 ▼a(MiAaPQ)AAI31334517
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aKarim, Rezwana.▼0(orcid)0000-0001-5445-417X
■24510▼aNutrient Stress Induced Lipid Metabolism: Exploring the SIRT2-ACSS2 Intersection
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a108 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Lin, Hening.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aMammalian cells possess intricate mechanisms to adapt to malnutrition and starvation, with de novo lipogenesis (DNL) emerging as a pivotal pathway during stress. This thesis explores the regulation of lipid metabolism under nutrient stress, focusing on the interplay between Sirtuin 2 (SIRT2) and Acetyl-CoA Synthetase 2 (ACSS2).In Chapter 1, I provide an overview of acetyl-CoA's role in lipogenesis, highlighting its various sources and use in fatty acid synthesis and histone acetylation. Specifically, I explore the regulatory roles of ACSS2 and SIRT2 in lipogenesis, laying the foundation for understanding how cells manage nutrient stress, particularly amino acid deficiency.Chapter 2 explores how SIRT2, ACSS2, and lipid metabolism interact during times of nutrient stress, particularly amino acid deficiency We reveal a novel mechanism wherein SIRT2 catalyzes the deacetylation of ACSS2 at lysine residue K271, resulting in ubiquitination and degradation of ACSS2 by the proteasome. Substitution of K271 leads to reduced ubiquitination of ACSS2, higher levels of ACSS2 protein, and enhanced lipogenesis, revealing a cellular mechanism for the efficient regulation of lipogenesis under nutrient stress.In Chapter 3, we establish a nuclear role for the SIRT2-ACSS2 axis. Through qPCR analysis and functional assays, our study demonstrates that SIRT2 knockdown elevates the expression of key lipogenic genes, Fatty Acid Synthase (FASN) and Acetyl-CoA Carboxylase Alpha (ACACA). Moreover, inhibition of ACSS2 attenuates the upregulation of FASN induced by SIRT2 depletion, indicating a functional link between SIRT2, ACSS2, and FASN expression. These results are important in the field of cancer biology, as changes in FASN expression due to acetate supplementation closely resemble those caused by SIRT2 modulation in different cancer cell types.
■590 ▼aSchool code: 0058.
■650 4▼aBiochemistry
■650 4▼aCellular biology
■650 4▼aBiology
■650 4▼aMolecular biology
■653 ▼aNutrient stress
■653 ▼aLipid metabolism
■653 ▼aMammalian cells
■653 ▼aFatty Acid Synthase
■690 ▼a0487
■690 ▼a0379
■690 ▼a0306
■690 ▼a0307
■71020▼aCornell University▼bBiochemistry, Molecular and Cell Biology.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162609▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
