Picture

Northwestern Medicine
​Breakthroughs for Physicians

​​
  • Home
  • Specialties
    • Cardiovascular >
      • Research
      • Clinical Breakthroughs
      • News
    • Endocrinology >
      • Clinical Breakthroughs In Endocrinology
      • Research In Endocrinology
      • News
    • ENT (Otolaryngology) >
      • Clinical Breakthroughs
      • Research
      • News
    • Gastroenterology >
      • Clinical Breakthroughs
      • Research
      • News
    • Geriatrics >
      • Clinical Breakthroughs
      • Research
      • News
    • Neurosciences >
      • Rare and Complex Brain Tumors
      • Research
      • COVID-19 and Neurosciences
      • News
      • Clinical Breakthroughs
    • OB-GYN >
      • Clinical Breakthroughs
      • Research
      • News
    • Oncology >
      • Clinical Breakthroughs
      • Research
      • News
    • Ophthalmology >
      • Clinical Breakthroughs
      • Research
      • News
    • Organ Transplant >
      • Clinical Breakthroughs
      • Research
      • News
    • Orthopaedics >
      • Clinical Breakthroughs
      • Research
      • News
    • Psychiatry >
      • Clinical Breakthroughs
      • Research
      • News
    • Pulmonary >
      • Clinical Breakthroughs
      • Research
      • News
    • Rehabilitation >
      • Clinical Breakthroughs
      • News
    • Rheumatology >
      • Clinical Breakthroughs
      • Research
      • News
    • Urology >
      • Clinical Breakthroughs
      • Research
      • News
  • CME
  • REFERRALS
    • Refer to NM Cardiovascular
    • Refer to NM Neurosciences
    • Refer to Other Specialties

< BACK TO RESEARCH IN NEUROSCIENCES

Tiled image of a single neuron compared to HeLa cells

April 2021

NEUROSCIENCES

INTERACTION OF MITOCHONDRIA AND LYSOSOMES KEY IN PARKINSON'S DISEASE

Featuring: Dimitri Krainc, MD, PhD
​
​Northwestern Medicine scientists have identified the consequences of contact between the mitochondria and the lysosome in the axons and synapses of human neurons, according to a study published in Nature Communications.

Prolonged contact, observed in neurons modeling Parkinson’s disease, caused aberrant distribution of mitochondria, contributing to the disease’s neuronal dysfunction. Investigators traced this phenomenon to mutations in the lysosomal enzyme β-glucocerebrosidase (GBA), according to Dimitri Krainc, MD, PhD, chair and the Aaron Montgomery Ward Professor of Neurology and senior author of the study.

“Our study is the first to demonstrate that mitochondria-lysosome contact sites dynamically form in mammalian neurons and are misregulated in Parkinson’s disease, leading to downstream pathogenic events,” said Krainc, who is also director of the Simpson Querrey Center for Neurogenetics.

Parkinson’s disease is among the most common neurodegenerative disorders, in which dopaminergic neurons in the substantia nigra brain region begin to die, causing loss of motor control. There are currently no disease-modifying therapies for Parkinson’s disease, so studying key pathways involved in pathogenesis is vital to identify therapeutic targets, Krainc said.

Recent studies from the Krainc laboratory — published in Nature and Science — have highlighted the role of mitochondrial and lysosomal dysfunction in Parkinson’s disease, suggesting that direct signaling between these two organelles may represent an important component of the disease.

In the current study, Soojin Kim, a fifth-year student in the Northwestern University Interdepartmental Neuroscience (NUIN) Program and lead author of the study, used super-resolution time-lapse microscopy to observe mitochondria and lysosomes in contact with each other throughout the dendrites and axons of nerve cells from patients with Parkinson’s disease. Importantly, she also discovered that neurons harboring loss-of-function mutations in GBA — considered one of the most serious risk factors for Parkinson’s disease — also significantly prolonged mitochondria-lysosome contact compared to normal neurons.

“This suggests that misregulation of mitochondria-lysosome contacts is an important step of disease pathogenesis,” Krainc said.

Digging deeper, the investigators found that mutant GBA in patient neurons alters important mediators of mitochondrial-lysosome contact, resulting in fewer mitochondria in the axons of neurons and lowered levels of ATP, the source of energy for cells.

Surprisingly, these downstream effects were rescued by upregulating the TBC1D15 protein, which is involved in mitochondria-lysosome tethering.

“When we knockdown TBC1D15 in healthy neurons, we see the phenotypes we’ve observed in diseased neurons,” Kim said. “When we overexpress TBC1D15 in diseased neurons, we could partially rescue downstream pathological phenotypes.”

These findings highlight mitochondrial-lysosomal contacts as an upstream regulator of mitochondrial function and the complex dynamics driving neurodegeneration in Parkinson’s disease, according to Krainc.

“Understanding the role and regulation of inter-organelle contacts has critical implications for multiple neurodegenerative diseases, and offers an important previously unstudied angle for understanding the convergence of mitochondrial and lysosomal dysfunction in Parkinson’s disease etiology,” Krainc said.

This study was supported by National Institutes of Health National Institute of Neurological Disorders and Stroke grants F32 NS101778, K99 NS109252, R01 NS076054 and R37NS096241, and a Warren Alpert Distinguished Scholars Fellowship Award.

This article was originally published in the Northwestern University Feinberg School of Medicine News Center on April 16, 2021. 
Headshot of Dr. Dimitri Krainc
Dimitri Krainc, MD, PhD, chair and the Aaron Montgomery Ward Professor and chair of The Ken and Ruth Davee Department of Neurology, was senior author of a study published in Nature Communications.

Refer a Patient

Northwestern Medicine welcomes the opportunity to collaborate with you on the care of your patients. 
Call 844.344.6663
Find an NM Neurologist
Find an NM Neurosurgeon
Find an NM Neuroradiologist

You May Also Like

Confocal micrographs

April 2021

NEUROSCIENCES
Mapping Neural Connections in Parkinson’s Disease
Alpha-synucleain pathology in cholinergic pedunculopontine neurons

December 2020

NEUROSCIENCES
New Developments in Parkinson's Pathology
Nerve cell in the direct pathway which contains a mutated version of LRRK2

November 2020

NEUROSCIENCES
Uncovering the Impact of Protein Mutations in Parkinson's

Northwestern Medicine Breakthroughs for Physicians

About Us     Terms of Use     Privacy Policy     How to Vote for U.S. News & World Report Best Hospitals
© 2025 Northwestern Medicine® and Northwestern Memorial HealthCare. 
Northwestern Medicine® is a trademark of Northwestern Memorial HealthCare, used by Northwestern University
Connect with us
[email protected]
International physicians, contact [email protected]
  • Home
  • Specialties
    • Cardiovascular >
      • Research
      • Clinical Breakthroughs
      • News
    • Endocrinology >
      • Clinical Breakthroughs In Endocrinology
      • Research In Endocrinology
      • News
    • ENT (Otolaryngology) >
      • Clinical Breakthroughs
      • Research
      • News
    • Gastroenterology >
      • Clinical Breakthroughs
      • Research
      • News
    • Geriatrics >
      • Clinical Breakthroughs
      • Research
      • News
    • Neurosciences >
      • Rare and Complex Brain Tumors
      • Research
      • COVID-19 and Neurosciences
      • News
      • Clinical Breakthroughs
    • OB-GYN >
      • Clinical Breakthroughs
      • Research
      • News
    • Oncology >
      • Clinical Breakthroughs
      • Research
      • News
    • Ophthalmology >
      • Clinical Breakthroughs
      • Research
      • News
    • Organ Transplant >
      • Clinical Breakthroughs
      • Research
      • News
    • Orthopaedics >
      • Clinical Breakthroughs
      • Research
      • News
    • Psychiatry >
      • Clinical Breakthroughs
      • Research
      • News
    • Pulmonary >
      • Clinical Breakthroughs
      • Research
      • News
    • Rehabilitation >
      • Clinical Breakthroughs
      • News
    • Rheumatology >
      • Clinical Breakthroughs
      • Research
      • News
    • Urology >
      • Clinical Breakthroughs
      • Research
      • News
  • CME
  • REFERRALS
    • Refer to NM Cardiovascular
    • Refer to NM Neurosciences
    • Refer to Other Specialties