Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis.

ABSTRACT: Impaired spermatogenesis and male infertility are common manifestations associated with mitochondrial diseases, yet the underlying mechanisms linking these conditions remain elusive. In this study, we demonstrate that mice deficient for the mitochondrial intra-membrane rhomboid protease PARL, a recently reported model of the mitochondrial encephalopathy Leigh syndrome, develop early testicular atrophy caused by a complete arrest of spermatogenesis during meiotic prophase I, followed by degeneration and death of arrested spermatocytes. This process is independent of neurodegeneration. Interestingly, genetic modifications of PINK1, PGAM5, and TTC19 - three major substrates of PARL with important roles in mitochondrial homeostasis - fail to reproduce or modify this severe phenotype, indicatin

SUBMITTER: Radaelli E 

PROVIDER: S-EPMC10519710 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature