Upregulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain

• DOI: 10.1016/j.jbc.2024.107403
• Publication Date: 2024-05-21T06:43:28Z
• Authors: Francesco Agostini; Leonardo Pereyra; Justin Dale; King Faisal Yambire; Silvia Maglioni; Alfonso Schiavi; Natascia Ventura; Ira Milosevic; Nuno Raimundo
• Keywords: Mitochondrial respiratory chain; Chain (unit)

Mitochondria and lysosomes are two organelles that carry out both signaling metabolic roles in cells. Recent evidence has shown mitochondria dependent on one another, as primary defects cause secondary the other. Although there functional impairments cases, consequences of mitochondrial dysfunction lysosomal dissimilar. Here, we used RNA sequencing to obtain transcriptomes from cells with or identify global cellular associated dysfunction. We these data determine pathways affected by organelles, which revealed a prominent role for cholesterol synthesis pathway. observed transcriptional upregulation this pathway murine models defects, while it is transcriptionally downregulated defects. identified posttranscriptional regulation transcription factor SREBF1, master regulator lipid biosynthesis, respiratory chain deficiency. Furthermore, found retention Ca