NDP52 interacts with mitochondrial RNA poly(A) polymerase to promote mitophagy

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• Mitophagy is a crucial cellular quality control process for removing damaged mitochondria.
• Autophagy receptors, like NDP52, mediate the recognition and engulfment of damaged mitochondria by autophagosomes.
• The precise function of NDP52's SKICH domain in mitophagy remained largely undefined.

Purpose of the Study:

• To elucidate the role of the NDP52 SKICH domain in mitophagy.
• To identify novel interaction partners of NDP52 involved in mitochondrial quality control.
• To understand how NDP52 contributes to the selective removal of damaged mitochondria.

Main Methods:

• Investigated NDP52 interactions using co-immunoprecipitation and cellular assays.
• Utilized mitophagy induction models with mitochondrial uncouplers.
• Assessed the impact of MTPAP depletion on NDP52-mediated mitophagy and LC3 recruitment.

Main Results:

• The SKICH domain of NDP52 directly interacts with mitochondrial RNA poly(A) polymerase (MTPAP).
• NDP52-MTPAP interaction occurs on depolarized mitochondria, dependent on the proteasome but not ubiquitin.
• Loss of MTPAP impairs NDP52-mediated mitophagy, and the complex enhances LC3 recruitment.

Conclusions:

• NDP52 and MTPAP form a novel autophagy receptor complex that enhances mitophagy.
• This complex facilitates the efficient autophagic elimination of damaged mitochondria.
• The NDP52-MTPAP interaction represents a key mechanism in mitochondrial quality control.