Harnessing Yeast Mitochondria for the Sustainable Production of High-Value Chemicals

In microbial cytoplasmic reaction compartments, competitive pathways and metabolic interactions often hinder the efficient synthesis of target compounds. In contrast, eukaryotic cells can control metabolic complexity by utilizing organelles to segregate biochemical pathways. Mitochondria, known as the "powerhouses of the cell," are rich in a unique set of enzymes, intermediate metabolites, and cofactors that can be exploited for metabolic engineering. However, wider application of mitochondria in metabolic engineering is limited by an insufficient understanding of their unique metabolic traits, the lack of efficient genetic tools, and the difficulty of balancing cell growth and product accumulation. This review outlines yeast mitochondria-related aspects, including their intrinsic properties, mechanisms of protein synthesis and import, recognition and screening of mitochondrial signal peptides, and potential advantages of using mitochondria alone or mitochondria collaborating with other organelles to produce high-value chemicals. Additionally, we discuss challenges in mitochondrial engineering and provide an outlook on future priorities.