Journal
CELL REPORTS
Volume 34, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108689
Keywords
-
Categories
Funding
- NIH [K08-AR075846, T32-AR007465, P30AR075043, R01-AR060802, R35GM126950, R37-NS060698]
- Dermatology Foundation
- National Psoriasis Foundation
- American Skin Association
- La Roche-Posay North American Foundation
- Penn Skin Biology & Disease Resource-Based Center [NIH P30-AR069589]
Ask authors/readers for more resources
This study reveals that regulated breakdown of mitochondria is critical for epidermal development, with keratinocytes in the upper layers initiating mitochondrial fragmentation, depolarization, and acidification. The mitophagy receptor NIX and DRP1 play essential roles in driving epidermal morphogenesis by promoting mitochondrial degradation in the terminal differentiation of keratinocytes.
The epidermis regenerates continually to maintain a protective barrier at the body's surface composed of differentiating keratinocytes. Maturation of this stratified tissue requires that keratinocytes undergo wholesale organelle degradation upon reaching the outermost tissue layers to form compacted, anucleate cells. Through live imaging of organotypic cultures of human epidermis, we find that regulated breakdown of mitochondria is critical for epidermal development. Keratinocytes in the upper layers initiate mitochondrial fragmentation, depolarization, and acidification upon upregulating the mitochondrion-tethered autophagy receptor NIX. Depleting NIX compromises epidermal maturation and impairs mitochondrial elimination, whereas ectopic NIX expression accelerates keratinocyte differentiation and induces premature mitochondrial fragmentation via the guanosine triphosphatase (GTPase) DRP1. We further demonstrate that inhibiting DRP1 blocks NIX-mediated mitochondrial breakdown and disrupts epidermal development. Our findings establish mitochondrial degradation as a key step in terminal keratinocyte differentiation and define a pathway operating via the mitophagy receptor NIX in concert with DRP1 to drive epidermal morphogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available