Work

ATP Citrate Lyase in Lipid Metabolism: Comparative Insights Across Eukaryotes with Emphasis on Yarrowia lipolytica

Year: 2025

Type: article

Abstract: ATP citrate lyase (ACL) is a highly conserved enzyme across eukaryotes that catalyzes the generation of cytosolic acetyl-CoA from citrate—a pivotal step linking central carbon metabolism to lipid biosynthesis. In the oleaginous yeast Yarrowia lipolytica, ACL is encoded by two genes, ACL1 and ACL2, forming a heteromeric complex that mirrors the multidomain architecture of the single-chain ACL enzymes found in mammals and plants. This conservation of catalytic architecture reflects a shared catalytic strategy across kingdoms, underscoring ACL’s fundamental role in metabolic integration. In Y. lipolytica, ACL is essential for directing mitochondrial citrate toward acetyl-CoA production and subsequent lipid accumulation. Yet, in contrast to well-characterized ACLs in animals and plants, the functional mechanisms and regulation of yeast ACL remain incompletely understood. A deeper understanding of ACL in Y. lipolytica offers not only evolutionary insights but also potential avenues for engineering lipid overproduction in microbial systems.

Source: Lipidology

DOI: 10.3390/lipidology2040020

Authors: Stylianos Fakas, Ayodeji Odunsi

Institution: Alabama Agricultural and Mechanical University

Language: English

Topic: Lipid metabolism and biosynthesis

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $1,207

Funders: U.S. Department of Agriculture, National Institute of Food and Agriculture