Characterization of Mitochondrial Ultrastructure and Immune Response in Parl-Deficient Fibroblasts

MMitochondria play a pivotal role in cellular metabolism and signalling, with their ultrastructure intimately tied to both energy production and innate immune responses. This study investigates the impact of PARL (Presenilin-associated rhomboid-like protein), an inner mitochondrial membrane protease proved to have multiple roles in mitochondrial physiology, on cristae architecture and immune priming, through the cGAS-STING axis-mediated interferon (IFN) response, in fibroblasts derived from wild-type (WT) and PARL-knockout (PARL-KO) mice. TEM (transmission electron microscopy) qualitative and quantitative analyses highlighted a role for PARL in modulating mitochondrial ultrastructure in fibroblasts at a steady state, which may have broader implications for cellular function, metabolism and stress responses. However, attempts to link these structural alterations to immune signalling failed, as they revealed no significant activation of the immune response, as assessed by gene expression analyses of key type-I IFN genes and immunoblotting of cGAS-STING downstream signalling components. Given PARL’s role in modulating the ultrastructure at mitochondria also in other tissues, further studies are warranted to explore the mechanisms underlying these observations and their possible relevance in physiological and pathological contexts.

Mitochondria play a pivotal role in cellular metabolism and signalling, with their ultrastructure intimately tied to both energy production and innate immune responses. This study investigates the impact of PARL (Presenilin-associated rhomboid-like protein), an inner mitochondrial membrane protease proved to have multiple roles in mitochondrial physiology, on cristae architecture and immune priming, through the cGAS-STING axis-mediated interferon (IFN) response, in fibroblasts derived from wild-type (WT) and PARL-knockout (PARL-KO) mice. TEM (transmission electron microscopy) qualitative and quantitative analyses highlighted a role for PARL in modulating mitochondrial ultrastructure in fibroblasts at a steady state, which may have broader implications for cellular function, metabolism and stress responses. However, attempts to link these structural alterations to immune signalling failed, as they revealed no significant activation of the immune response, as assessed by gene expression analyses of key type-I IFN genes and immunoblotting of cGAS-STING downstream signalling components. Given PARL’s role in modulating the ultrastructure at mitochondria also in other tissues, further studies are warranted to explore the mechanisms underlying these observations and their possible relevance in physiological and pathological contexts.