PT  - JOURNAL ARTICLE
AU  - Ilamathi, Hema Saranya
AU  - Benhammouda, Sara
AU  - Lounas, Amel
AU  - Al-Naemi, Khalid
AU  - Desrochers-Goyette, Justine
AU  - Lines, Matthew A.
AU  - Richard, François J.
AU  - Vogel, Jackie
AU  - Germain, Marc
TI  - Contact sites between endoplasmic reticulum sheets and mitochondria regulate mitochondrial DNA replication and segregation
AID  - 10.1101/2021.12.09.472002
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.12.09.472002
4099  - http://biorxiv.org/content/early/2022/11/29/2021.12.09.472002.short
4100  - http://biorxiv.org/content/early/2022/11/29/2021.12.09.472002.full
AB  - Mitochondria are multi-faceted organelles crucial for cellular homeostasis that contain their own genome. Mitochondrial DNA (mtDNA) codes for several essential components of the electron transport chain, and mtDNA maintenance defects lead to mitochondrial diseases. mtDNA replication occurs at endoplasmic reticulum (ER)-mitochondria contact sites and is regulated by mitochondrial dynamics. Specifically, mitochondrial fusion is essential for mtDNA maintenance. In contrast, while loss of mitochondrial fission causes the aggregation of nucleoids (mtDNA-protein complexes), its role in nucleoid distribution remains unclear. Here, we show that contact sites between mitochondria and ER sheets, the ER structure associated with protein synthesis, regulate mtDNA replication and nucleoid distribution within mitochondrial networks. Specifically, DRP1 loss or mutation leads to altered ER sheets and enhanced physical interaction with mitobulbs, mitochondrial structures containing aggregated nucleoids. Importantly, nucleoid distribution and mtDNA replication were rescued by expressing the ER sheet protein CLIMP63. Thus, our work identifies a novel role of ER sheets-mitochondria contact sites in regulating mtDNA replication and distribution.Competing Interest StatementThe authors have declared no competing interest.