Mipep deficiency in adipocytes impairs mitochondrial protein maturation and leads to systemic inflammation and metabolic dysfunctions DOI Creative Commons
Yuka Nozaki, Masaki Kobayashi,

Tomoyoshi Fukuoh

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 14, 2025

Most mitochondrial proteins encoded in the nuclear genome are synthesized cytoplasm. These subsequently undergo maturation through cleavage of a signal sequence at N-terminus by one or two peptidases, which is essential for their function within mitochondria. The present study demonstrates that adipocyte-specific knockout peptidase, intermediate peptidase (MIPEP), resulted disordered proteostasis MIPEP substrate and defective maturation. deficiency white brown adipocytes suppressed expression adipocyte differentiation, lipid metabolism, biogenesis genes. alterations led to lipoatrophy adipose tissue whitening tissue. Additionally, it induced an atypical unfolded protein response local inflammation Furthermore, fatty liver splenomegaly caused systemic impairments glucose metabolism inflammation. findings indicate defects certain subsequent disorders cause chronic inflammatory metabolic dysfunctions.

Language: Английский

Mipep deficiency in adipocytes impairs mitochondrial protein maturation and leads to systemic inflammation and metabolic dysfunctions DOI Creative Commons
Yuka Nozaki, Masaki Kobayashi,

Tomoyoshi Fukuoh

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 14, 2025

Most mitochondrial proteins encoded in the nuclear genome are synthesized cytoplasm. These subsequently undergo maturation through cleavage of a signal sequence at N-terminus by one or two peptidases, which is essential for their function within mitochondria. The present study demonstrates that adipocyte-specific knockout peptidase, intermediate peptidase (MIPEP), resulted disordered proteostasis MIPEP substrate and defective maturation. deficiency white brown adipocytes suppressed expression adipocyte differentiation, lipid metabolism, biogenesis genes. alterations led to lipoatrophy adipose tissue whitening tissue. Additionally, it induced an atypical unfolded protein response local inflammation Furthermore, fatty liver splenomegaly caused systemic impairments glucose metabolism inflammation. findings indicate defects certain subsequent disorders cause chronic inflammatory metabolic dysfunctions.

Language: Английский

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