‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p<0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

Background: Evidence suggests that children and young people (CYP) who present to the emergency department (ED) for mental health (MH) difficulties may have extended lengths of stay (LOS); however, there is a paucity of research in Australia regarding the factors associated with extended LOS. This study aimed to determine the factors associated with extended LOS for paediatric MH-related presentations to the EDs in South Western Sydney (SWS), a multicultural community in Australia. Methods: We analysed electronic medical records (eMR) of 7,409 MH-related ED encounters of CYP aged 0 up to 18 years from all six public hospitals in SWS from January 2016 to April 2022. Extended LOS was defined as encounters of more than 4 hours. We assessed factors associated with extended LOS using a multilevel logistic regression model, accounting for hospital-level clustering. Results: Approximately 57.6% of all ED presentations for paediatric MH involved extended LOS. ED presentations by adolescents (adjusted odds ratio (AOR) 2.23, 95% CI 1.20-4.17 for 12-14 years and AOR 2.69, 95% CI 1.44-5.00 for 15-17 years), and patients with a preferred language other than English (AOR 1.47, 95% CI 1.15-1.89) had increased odds of extended LOS compared to their counterparts. Deliberate self-harm related presentations, the most commonly presented MH condition, had higher odds of extended LOS than other MH-related presentations (AOR 1.77, 95% CI 1.59-1.98). Patients with MH presentations that required urgent evaluation (triage levels 1-2) had higher odds of extended LOS (AOR 1.38, 95% CI 1.15-1.65) compared to triage level 3, whereas those with triage levels 4-5 had lower odds (AOR 0.66, 95% CI 0.58-0.74). Further, patients with MH-related presentations that came by ambulance (compared to other mode of presentations) and presentations that happened at night and late at night (compared to early morning and daytime presentations). The odds of extended LOS were considerably lower during the COVID-19 period compared to the pre-COVID-19 period (AOR 0.74, 95% CI 0.67-0.82). Additionally, extended paediatric LOS for MH issues in the ED showed notable hospital-level heterogeneity. Conclusion: A large proportion of extended LOS in ED and sociodemographic disparities reflect inequality in access to paediatric MH care. Our findings highlight the need for equitable distribution of resources directed towards at-risk CYP to improve MH outcomes and reduce health system burden.