MTFP1 controls mitochondrial fusion to regulate inner membrane quality control and maintain mtDNA levels.
Cell
; 187(14): 3619-3637.e27, 2024 Jul 11.
Article
in En
| MEDLINE
| ID: mdl-38851188
ABSTRACT
Mitochondrial dynamics play a critical role in cell fate decisions and in controlling mtDNA levels and distribution. However, the molecular mechanisms linking mitochondrial membrane remodeling and quality control to mtDNA copy number (CN) regulation remain elusive. Here, we demonstrate that the inner mitochondrial membrane (IMM) protein mitochondrial fission process 1 (MTFP1) negatively regulates IMM fusion. Moreover, manipulation of mitochondrial fusion through the regulation of MTFP1 levels results in mtDNA CN modulation. Mechanistically, we found that MTFP1 inhibits mitochondrial fusion to isolate and exclude damaged IMM subdomains from the rest of the network. Subsequently, peripheral fission ensures their segregation into small MTFP1-enriched mitochondria (SMEM) that are targeted for degradation in an autophagic-dependent manner. Remarkably, MTFP1-dependent IMM quality control is essential for basal nucleoid recycling and therefore to maintain adequate mtDNA levels within the cell.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Mitochondrial
/
Mitochondrial Proteins
/
Mitochondrial Membranes
/
Mitochondrial Dynamics
/
Mitochondria
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell
Year:
2024
Document type:
Article
Country of publication: