Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events.

While extensive work has examined the mechanisms of mitochondrial fission, it remains unclear whether internal mitochondrial proteins in metazoans play a direct role in the process. Previously, the yeast inner membrane protein Mdm33 was shown to be required for normal mitochondrial morphology and has been hypothesized to be involved in mitochondrial fission. However, it is unknown whether Mdm33 plays a direct role, and it is not thought to have a mammalian homolog.

The Detection of Xylazine in Tijuana, Mexico: Triangulating Drug Checking and Clinical Urine Testing Data.

Introduction: Xylazine is a veterinary anesthetic increasingly present alongside illicit fentanyl in the US and Canada, presenting novel health risks. Although xylazine remains less common in the Western US, Mexican border cities serve as key trafficking hubs and may have higher prevalence of novel substances, but surveillance has been limited.

Methods: We examined deidentified records from the Prevencasa harm reduction clinic in Tijuana, describing urine and paraphernalia testing from patients reporting using illicit opioids within 24 hr.

Illicit Fentanyl Use and Hepatitis C Virus Seroconversion Among People Who Inject Drugs in Tijuana and San Diego: Results From a Binational Cohort Study.

Background: Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts hepatitis C virus (HCV) and human immunodeficiency virus (HIV) incidence among a cohort of people who inject drugs (PWID) in San Diego, California and Tijuana, Mexico.

Methods: PWID were recruited during 2020-2022, undergoing semi-annual interviewer-administered surveys and HIV and HCV serological rapid tests through 2024.

Dual-localized PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX.

PPTC7 is a mitochondrial-localized phosphatase that suppresses BNIP3- and NIX-mediated mitophagy, but the mechanisms underlying this regulation remain ill-defined. Here, we demonstrate that loss of PPTC7 upregulates BNIP3 and NIX post-transcriptionally and independent of HIF-1α stabilization. Loss of PPTC7 prolongs the half-life of BNIP3 and NIX while blunting their accumulation in response to proteasomal inhibition, suggesting that PPTC7 promotes the ubiquitin-mediated turnover of BNIP3 and NIX.

Compositionally unique mitochondria in filopodia support cellular migration.

Local metabolic demand within cells varies widely and the extent to which individual mitochondria can be specialized to meet these functional needs is unclear. We examined the subcellular distribution of MICOS, a spatial and functional organizer of mitochondria, and discovered that it dynamically enriches at the tip of a minor population of mitochondria in the cell periphery that we term "METEORs". METEORs have a unique composition; MICOS enrichment sites are depleted of mtDNA and matrix proteins and contain high levels of the Ca uniporter MCU, suggesting a functional specialization.

Leveraging pooled medical examiner records to surveil complex and emerging patterns of polysubstance use in the United States.

Background: The United States (US) is an extreme global outlier for drug-related death rates. However, data describing drug-related deaths are generally available only on an 8-13-month lag. Furthermore, granular details about substance-involvement are often not available, which particularly stymies efforts to track fatal polysubstance and novel psychoactive substance use.

Understanding and Addressing Widening Racial Inequalities in Drug Overdose.

The fourth wave of the United States overdose crisis-driven by the polysubstance use of fentanyl with stimulants and other synthetic substances-has driven sharply escalating racial/ethnic inequalities in drug overdose death rates. Here the authors present a detailed portrait of the latest overdose trends and synthesize the literature to describe where, how, and why these inequalities are worsening. By 2022 overdose deaths among Native and Black Americans rose to 1.

A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

Background: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California.

Methods: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting.

Global Assessment of Palliative Care Need: Serious Health-Related Suffering Measurement Methodology.

Context: Inequities and gaps in palliative care access are a serious impediment to health systems especially in low- and middle-income countries and the accurate measurement of need across health conditions is a critical step to understanding and addressing the issue. Serious Health-related Suffering (SHS) is a novel methodology to measure the palliative care need and was originally developed by The Lancet Commission on Global Access to Palliative Care and Pain Relief. In 2015, the first iteration - SHS 1.

Human CCDC51 and yeast Mdm33 are functionally conserved mitochondrial inner membrane proteins that demarcate a subset of organelle fission events.

Mitochondria are highly dynamic double membrane-bound organelles that exist in a semi-continuous network. Mitochondrial morphology arises from the complex interplay of numerous processes, including opposing fission and fusion dynamics and the formation of highly organized cristae invaginations of the inner membrane. While extensive work has examined the mechanisms of mitochondrial fission, it remains unclear how fission is coordinated across two membrane bilayers and how mitochondrial inner membrane organization is coupled with mitochondrial fission dynamics.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020 to 2023.

Background: Amidst a rapidly evolving drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking heroin, fentanyl and methamphetamine among a cohort of people who injected drugs at baseline from San Diego, California.

Methods: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting.

PPTC7 limits mitophagy through proximal and dynamic interactions with BNIP3 and NIX.

PPTC7 is a mitochondrial-localized PP2C phosphatase that maintains mitochondrial protein content and metabolic homeostasis. We previously demonstrated that knockout of elevates mitophagy in a BNIP3- and NIX-dependent manner, but the mechanisms by which PPTC7 influences receptor-mediated mitophagy remain ill-defined. Here, we demonstrate that loss of PPTC7 upregulates BNIP3 and NIX post-transcriptionally and independent of HIF-1α stabilization.

Drug overdose mortality rates by educational attainment and sex for adults aged 25-64 in the United States before and during the COVID-19 pandemic, 2015-2021.

Introduction: Dramatic increases in U.S. drug overdose deaths involving synthetic opioids, especially fentanyl, beginning around 2014 have driven a marked progression in overall drug overdose deaths in the U.

A DRP-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial inner membrane-localized MICOS complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae shaping factors, has not been fully determined.

PPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy.

PPTC7 is a resident mitochondrial phosphatase essential for maintaining proper mitochondrial content and function. Newborn mice lacking Pptc7 exhibit aberrant mitochondrial protein phosphorylation, suffer from a range of metabolic defects, and fail to survive beyond one day after birth. Using an inducible knockout model, we reveal that loss of Pptc7 in adult mice causes marked reduction in mitochondrial mass and metabolic capacity with elevated hepatic triglyceride accumulation.

Deep Learning Models Capture Histological Disease Activity in Crohn's Disease and Ulcerative Colitis with High Fidelity.

Background And Aims: Histological disease activity in inflammatory bowel disease [IBD] is associated with clinical outcomes and is an important endpoint in drug development. We developed deep learning models for automating histological assessments in IBD.

Methods: Histology images of intestinal mucosa from phase 2 and phase 3 clinical trials in Crohn's disease [CD] and ulcerative colitis [UC] were used to train artificial intelligence [AI] models to predict the Global Histology Activity Score [GHAS] for CD and Geboes histopathology score for UC.

Completion of mitochondrial division requires the intermembrane space protein Mdi1/Atg44.

Mitochondria are highly dynamic double membrane-bound organelles that maintain their shape in part through fission and fusion. Mitochondrial fission is performed by a dynamin-related protein, Dnm1 (Drp1 in humans), that constricts and divides the mitochondria in a GTP hydrolysis-dependent manner. However, it is unclear whether factors inside mitochondria help coordinate the process and if Dnm1/Drp1 activity is sufficient to complete the fission of both mitochondrial membranes.

Longitudinal changes in co-involved drugs, comorbidities, and demographics of methamphetamine-related deaths in Los Angeles County.

Introduction: We conducted a population-based observational study of all medical examiner cases in Los Angeles County from January 2012 through June 2021 in which methamphetamine was listed as a cause of or contributing factor to death (n = 6125). We aimed to characterize demographics, comorbidities, and co-involved substances in methamphetamine-related deaths longitudinally in Los Angeles County, California.

Methods: We used detailed death record data to manually classify fatalities by involvement of each organ system, opioids, alcohol, cocaine, other drugs or medications, and external/traumatic causes.

An intermembrane space protein facilitates completion of mitochondrial division in yeast.

Mitochondria are highly dynamic double membrane-bound organelles that maintain their shape in part through fission and fusion. Mitochondrial fission is performed by the dynamin-related protein Dnm1 (Drp1 in humans), a large GTPase that constricts and divides the mitochondria in a GTP hydrolysis-dependent manner. However, it is unclear whether factors inside mitochondria help coordinate the process and if Dnm1/Drp1 activity alone is sufficient to complete fission of both mitochondrial membranes.

US drug overdose mortality rose faster among hispanics than non-hispanics from 2010 to 2021.

Background: Historically, overdose mortality rates among Hispanics have been lower than non-Hispanics. The purpose of this analysis was to characterize the U.S.