Mitochondria under the spotlight: On the implications of mitochondrial dysfunction and its connectivity to neuropsychiatric disorders

Zilocchi, Mara; Broderick, Kirsten; Phanse, Sadhna; Aly, Khaled A.; Babu, M. Madan

doi:10.1016/j.csbj.2020.09.008

Cited by 12 publications

(10 citation statements)

References 147 publications

(175 reference statements)

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“…Because BLM-s is localized in the mitochondria [ 31 ], depletion of BLM-s could potentially affect mitochondrial physiology in the limbic system, which in turn causes dysfunctional mood control. Further exploration of BLM-s’ role in mitochondria would be interesting, given that drugs targeting mitochondria physiology are currently investigated as a potential pharmaceutical target for the treatment-resistant major depressive disorder [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

et al. 2022

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Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s−/−) mouse. The Blm-s−/− mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s−/− mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s−/− mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s−/− DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression.

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Section: Discussionmentioning

confidence: 99%

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

et al. 2022

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“…Machine learning-based decision-making tools are also used to screen and discover new treatments/drugs to treat neuropsychiatric disorders by analyzing the different biomarkers (genetic and biochemical) and molecules to chemical reactions. This approach could also help identify the best treatment for each patient by analyzing the treatment response from each patient, so-called precision medicine (85).…”

Section: Machine Learning Tools For Future Studies and Therapeutic Treatment Developmentmentioning

confidence: 99%

Autism Spectrum Disorders: The Mitochondria Connection

Wen

Yao

2021

Autism Spectrum Disorders

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Autism spectrum disorders (ASD) are considered neurodevelopmental disorders characterized by restricted patterns of behavior and difficulties with communication and social interaction.Cumulative evidence suggests ASD have a wide range of co-occurring multisystemic conditions beyond the primary diagnosis. However, the etiology of ASD still eludes us. Finding a key cellular process responsible for the cognitive features, specific behaviors, and abnormalities in multiple systems presents major challenges to researchers. Mitochondria are multifaceted organelles involved in many cellular functions. The relationship between mitochondria and ASD has been studied for many years. Mitochondria may play a crucial role in ASD pathophysiology. By reviewing the connections between mitochondria and ASD from genes, pathways, biological activities, and clinical manifestations, we hope to provide clues for future studies that elucidate the biological basis of ASD symptoms and behaviors.

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“…To shed light on database overlaps and discrepancies, we have recently surveyed ( Zilocchi et al., 2020 ) five established databases ( Figure 1 A and Table S1 ) and extracted their mt protein inventory, including MitoCarta2.0 ( Calvo et al., 2016 ), Integrated Mitochondrial Protein Index (IMPI) ( Smith and Robinson, 2019 ), UniProt ( UniProt, 2019 ), Gene Ontology (GO) ( The Gene Ontology Consortium, 2019 ), and COMPARTMENTS ( Binder et al., 2014 ). Although databases such as IMPI and COMPARTMENTS share 1,197 mt proteins in common, MitoCarta2.0 and UniProt only share 877 mt proteins, with 647 proteins shared between all five databases ( Figure 1 A).…”

Section: A Systems Perspective Of Mt Proteins In Rdsmentioning

confidence: 99%

“…In addition, artificial intelligence is also being rapidly integrated to model diseased human cells, which can overcome the scarcity of RD samples. Examining these models can vary based on nutrient, lipid, and metabolite to suggest potential molecules of therapeutic value solely based on machine learning algorithms that stratify and match patients and prioritize in silico -examined therapeutic options ( Zilocchi et al., 2020 ). This can help clinicians involved in RDs to find their needle in the haystack, and with more contributions from the scientific and clinician community, more tools, methods, and databases can be developed to accelerate RD therapeutic developments.…”

Section: Genotypic and Phenotypic Matchmaking Toolsmentioning

confidence: 99%

From fuzziness to precision medicine: on the rapidly evolving proteomics with implications in mitochondrial connectivity to rare human disease

et al. 2021

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Mitochondria under the spotlight: On the implications of mitochondrial dysfunction and its connectivity to neuropsychiatric disorders

Abstract: Graphical abstract

Cited by 12 publications

References 147 publications

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

Autism Spectrum Disorders: The Mitochondria Connection

From fuzziness to precision medicine: on the rapidly evolving proteomics with implications in mitochondrial connectivity to rare human disease

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